Day :
- Track 1: Pre-formulation Considerations
Track 2: Formulation Aspects for Various Routes
Location: Melia Avenida America
Chair
Joel Richard
IPSEN, France
Co-Chair
Gabriele Sadowski
TU Dortmund, Germany
Session Introduction
Gabriele Sadowski
TU Dortmund, Germany
Title: Predicting the solubility advantage of amorphous pharmaceuticals
Time : 09:50-10:10
Biography:
Gabriele Sadowski is full Professor for Thermodynamics. Her main fields of research are thermodynamics of biological and pharmaceutical systems. She has published about 150 papers, is Chair of the German Working Party of Thermodynamics and member of the German Academy of Technical Sciences. 2011, she received the prestigious Leibniz award.
Abstract:
Due to their possible advantages in bioavailability, solubility and dissolution rate, amorphous pharmaceuticals gained great attention in drug development. However, so far there exists no reliable model to quantitatively describe and predict the solubility advantage of amorphous versus crystalline pharmaceuticals. In most cases, the calculated solubility advantages are orders of magnitudes higher than the measured ones. The objective of this work was to predict the solubility of amorphous pharmaceuticals using a thermodynamic approach. The Perturbed-Chain Statistical-Associating Fluid Theory (PC-SAFT) was used to calculate the solubility of amorphous and crystalline, poorly-soluble pharmaceuticals. In contrast to common approaches and in agreement with the real thermodynamic phase behavior, the amorphous pharmaceutical was not treated as a pure component being in equilibrium with the solvent. Instead, the proposed approach accounts for the fact the amorphous pharmaceutical –in contrast to the crystalline one- absorbs a certain amount of solvents which influences the chemical potential and therewith the solubility of the amorphous pharmaceutical. Moreover, the activity coefficients which account for the influence of the solvent on the solubility of both, the crystalline and the amorphous pharmaceutical, are accounted for and also calculated from PC-SAFT. The therewith calculated solubility advantage is therefore obtained not only as function of the pharmaceutical, but also of the solvent. Solubility advantages predicted using the proposed approach for a whole series of pharmaceuticals qualitatively agree with experimental data and are in all considered cases superior to results obtained from existing models.
Shilpa Raut
Amway, USA
Title: Formulation of nutraceuticals and dietary supplements: Formulation and regulatory challenges
Time : 10:10-10:30
Biography:
Shilpa Raut currently works at Nutrilite Health Institute (Amway) in the field of dietary supplement formulation where she is a part of the R&D group, involved in developing and bringing innovative science in the field of nutraceuticals. She completed her PhD in Pharmaceutics and Drug Design from MCPHS University in 2013. She has also been an Instructor for Pharmaceutics I & II courses at MCPHS University. She has few publications in journals and several poster presentations to her credit. She was awarded the IPEC Graduate Student Scholarship Award for excellence in excipient research. She is also on the Editorial Board of International Journal of Pharmaceutical Sciences: Open Access
Abstract:
The formulation of pharmaceutical quality dietary supplements that have adequate physical and chemical stability as well as are safe, cost effective and technologically feasible can entail numerous challenges. In contrast to drugs which are usually well defined chemical entities, botanicals are complex ingredients containing multiple chemical components and often several classes of compounds are present in a single product. Many of these compounds are unstable to heat, light, oxygen, alkaline pH and elevated humidity. They may also have poor flow, bulk density and variable particle size distribution. Thus successful development of nutraceuticals requires knowledge of the fundamental aspects of the physical and chemical properties of the various forms of the ingredients, the use of adequate techniques of manufacturing, selection of the right excipients and the addition of suitable manufacturing overages based upon critical stability studies. Regulatory requirements also pose challenges to the development of dietary supplements. Based on the ingredients and the claims, the formula can fit into different categories in different countries. Registration complexity and timing varies greatly by category and country with ever increasing scrutiny. In this oral presentation, I will talk about the formulation of dietary supplements and how it is similar and/or different from pharmaceutical formulations.
Tina Kauss
University of Bordeaux, France
Title: The role of preformulation in the choice of rectal formulation : case study of ceftriaxone
Time : 10:30-10:50
Biography:
Tina Kauss (PharmD at University of Bordeaux and Master 2 of Pharmaceutical technology and Biopharmacy at University Paris 11) completed her PhD in 2007 at Bordeaux’s University, followed by 3 years of postdoctoral studies in pharmaceutical development (pharmaceutical technology, biopharmacy and analytical chemistry). Since 2011 she is assistant professor of Pharmaceutical technology and Biopharmacy at the University of Bordeaux. She has published 16 papers in reputed journals of pharmaceutical development.
Abstract:
Ceftriaxone is a wide spectrum antibiotique currently existing as injectable powder for extemporaneous reconstitution before intreveinous or intramuscular administration. The aim of our project was to formulate rectal pediatric forms. Ceftriaxone belongs to Biopharmaceutical classification System (BCS) classe 3, meaning that it is well soluble, but weakly permeable. Furthermore, it is described as sensitive to degradation in several conditions. A large preformulation study was therefore conducted to define its processability and identify conditions leading to its degradation. The results of this study showed that ceftriaxone was not very hygroscopic, but adding water to formulation affects significantly its immediate and long term stability. When dried after wetting to simulate a granulation process, ceftriaxone content remained stable. However, surprisingly grinding and compaction/crushing induced ceftriaxone drug content decrease after 6 month of accelerated aging (40°C/75%RH), but not before. X-ray diffraction showed that ceftriaxone crystalline lattice could be affected by high (but not moderate) compression forces. This study was further completed by a preliminary compatibility study of binary mixtures of ceftriaxone and various excipients to further establish a ist of potential drug forms for further pharmaceutical development.
Biography:
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Abstract:
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Mino R. Caira
University of Cape Town, South Africa
Title: Physicochemical characterization of crystalline supramolecular systems containing established drugs and new drug candidates
Time : 11:05-11:25
Biography:
Mino Caira has directed the Centre for Supramolecular Chemistry Research at the University of Cape Town (UCT) since 2005. He retired as Professor of Physical Chemistry in 2014 and was subsequently appointed as a Senior Scholar in the Department of Chemistry at UCT. His expertise is in the area of solid-state chemistry of drug polymorphs and novel multi-component systems containing active pharmaceutical ingredients. He has published over 300 papers in international journals and since 2009 has served on the Editorial Advisory Board of the Journal of Pharmaceutical Sciences.
Abstract:
Crystalline supramolecular systems containing drug molecules, for example drug solvates, co-crystals and inclusion compounds, are enjoying increasing attention as they represent new multi-component forms whose pharmaceutically relevant properties (e.g. aqueous solubility, stability, developability) may be significantly more favourable than those of the untreated drug. In the case of established drugs, this could translate into extended patent life, while for new drug leads early intervention in generating such ‘supramolecular derivatives’ could facilitate the selection of the most promising contenders for further development. Physicochemical characterization of these multi-component crystalline phases to establish their stoichiometric composition, thermodynamic stabilities and structural nature at the molecular level is essential but can often pose more challenges than those encountered when dealing with single-component systems (e.g. polymorphically pure drugs). Such challenges may be associated with included solvent (e.g. content variability and structural disorder) and with difficulties in unequivocal assignment of the nature of heteromolecular interactions (e.g. distinguishing co-crystals and salts). This presentation will focus on the use of thermal analysis and X-ray diffraction methods on both powders and single crystals as fundamental techniques used to address these issues. Their application to supramolecular systems such as co-crystals of active pharmaceutical ingredients and cyclodextrin inclusion complexes of bioactive molecules will be illustrated. Closely related topics to be highlighted are the ubiquitous occurrence of crystal polymorphism for the systems in question and the limits of the utility of powder X-ray diffraction in phase identification.
Alessandra Maroni
University of Milan, Italy
Title: Swellable/erodible delivery systems for time-controlled release of drugs into the gastrointestinal tract
Time : 11:25-11:45
Biography:
Alessandra Maroni, PhD, is an Assistant Professor the University of Milan since 2002. Her main research interests are in the area of oral delivery and formulation. She is a peer reviewer for the leading journals in the field, serves on the Editorial Advisory Board of Journal of Pharmaceutical Sciences and is a member of the scientific societies CRS, CRS Italy Chapter, AFI, ADRITELF and SCI. She has authored over 50 publications, including journal articles, patent applications and book chapters, and more than 100 conference presentations.
Abstract:
In oral delivery, it is often advantageous to have the onset of drug release delayed for a programmable period of time following administration. This would indeed allow the chronotherapeutic needs of several pathologies with night or early morning symptoms to be addressed with no negative impact on patient compliance. Moreover, a lag time prior to release would enable targeting of the colon, as required by intestinal disease conditions or in the case of bioactive molecules that show poor stability and permeability in the upper intestine, such as biotechnological drugs. Delivery systems intended for time-controlled release, i.e. able to incorporate a lag phase in their release patterns, are often in the form of a drug-containing core enclosed in a functional polymeric barrier. In particular, swellable/erodible systems are provided with hydrophilic polymer barriers, most frequently coatings, that undergo progressive swelling and erosion when in contact with aqueous fluids. As a result, the time at which the drug starts being released from the core is postponed. The duration of the lag phase primarily depends on the physico-chemical properties of the polymer, above all the viscosity grade, and on the thickness of the layer applied. By affecting the structure of the latter, the manufacturing technique may also play a role, and a different outcome in terms of performance has been obtained by using double-compression, film-coating or hot-processing (injection-molding, 3D printing by fused deposition modeling). In this presentation, progress in the field of oral delivery systems for time-controlled release based on swellable/erodible polymers is outlined.
Tina Kauss
University of Bordeaux, France
Title: Rectal alternatives to existing oral and injectable pediatric antibiotherapies : going beyond a wax suppository
Time : 11:45-12:05
Biography:
Tina Kauss (PharmD at University of Bordeaux and Master 2 of Pharmaceutical technology and Biopharmacy at University Paris 11) completed her PhD in 2007 at Bordeaux’s University, followed by 3 years of postdoctoral studies in pharmaceutical development (pharmaceutical technology, biopharmacy and analytical chemistry). Since 2011 she is assistant professor of Pharmaceutical technology and Biopharmacy at the University of Bordeaux. She has published 16 papers in reputed journals of pharmaceutical development.
Abstract:
According to recent World Health Organization reports, bacterial infections still take a heavy morbidity and mortality toll on the lives of children, particularly those under 5 years of age, and particularly in developing countries. Against this scenario, there is a lack of paediatric formulations of antibiotics that are adapted to the needs of the developing world, where these infections are mostly prevalent. Formulations are needed that can be administered by unqualified personnel (non-injectable) to children who cannot take oral medications (non-per-os) because their conditions are deteriorating. Pharmaceutical development of rectal forms has gone far beyond the common fatty suppository and offers solutions for successful rectal delivery even in rural tropical zones, where fatty suppositories melt and are not administrable.This work shows, that rectal route can be considered as a valuable alternative for specific applications, such as pediatric antibiotherapy in developing countries. Several forms were considered and tested for azithromycin and ceftriaxone, namely PEG solid dispersion suppositories, gels, suspensions, self emulsifying drug delivery systems (SEDDS), grain or powder in hard gelatin capsules and rectodispersible tablets. The aim of this development was to propose a low cost prototype formulation of rectal pediatric antibiothepy, ready for industrial scale-up. The selection of formulations was based on their feasibility, stability in ICH conditions and their bioavailability. Solid dispersion PEG suppository appeared to be the optimal formulation of azithromycin and solid forms appeared promising for ceftriaxone.
Sonia Al-Qadi
Birzeit University, Palestine
Title: Inhalable powders loaded with chitosan nanoparticles for protein drug delivery
Time : 12:05-12:25
Biography:
Sonia Al-Qadi is assistant professor at Birzeit University, Palestine. She earned her MSc and PhD in pharmaceutical technology from Santiago de Compostela University, Spain. She worked as a postdoctoral fellow at the Department of Physics, Chemistry and Pharmacy, University of Southern Denmark and, then at the Department of Pharmacy, Copenhagen University. She thereafter worked as an assistant professor at the Faculty of Pharmacy, Isra University, Jordan. Her research interest focuses on nano-drug drug delivery systems, Biomaterials, and drug testing models. She has many publications and presented her research works in different international conferences as posters or oral presentations, besides serving as a reviewer for some international journals.
Abstract:
This work aimed at developing inhalable powders of insulin-loaded chitosan nanoparticles (INS-CS NPs), by microencapsulation method, and investigating their pulmonary absorption in vivo. To this end, INS-CS NPs were prepared by incorporating insulin (INS) into nanoparticlulate entities (NPs), consisting of the polysaccharide chitosan (CS) and the cross-linker sodium tripolyphosphate (TPP), usnig ionotropic gelation. Afterwards, INS-CS NPs were characterized with respect to morphology, size, zeta potential and loading capacity. Next, the inhalable powders were produced by co-spray drying the suspensions of INS-CS NPs with the sugar mannitol (thermoprotectant), resulting in microstructured powders with adequate aerodynamic properties for lung deposition. In vivo performance of INS-CS NPs spray-dried powders was assessed via monitoring plasma glucose levels, following intratracheal administration in rats. The spray-dried INS-CS NPs were successfully microencapsulated into mannitol microspheres, forming powders with appropriate aerodynamic properties for deep lung deposition. The IN-CS NPs/mannitol weight ratios as well as spray drying process parameters affected the properties of the microspheres obtained. Additionally, the NPs were easily recovered after reconstitution of the spray-dried powders in aqueous media. The in vivo study revealed that the microencapsulated INS-CS NPs induced a more pronounced and prolonged hypoglycaemic effect, as compared to the controls, including INS-loaded mannitol microspheres, native INS solution and the suspension of INS-CS NPs. Overall, besides the advantage of non-invasive administration and the desired stability of dry formulations, when compared to their liquid counterparts, inhalable micro/nanoparticulate systems may hold promise for lung delivery of therapeutic macromolecules for systemic or local effects (e.g., Cystic fibrosis, lung cancer).
Khalid Garba Mohammed
Bayero University, Nigeria
Title: Evaluation of filler/binder properties of modified starches derived from Plectranthus esculentus by direct compression in metronidazole tablets formulation
Time : 12:25-12:45
Biography:
Khalid G M has completed his first degree (BPharm) in 2012 from Ahmadu Bello University, Nigeria, and is currently pursuing his MSc in Pharmaceutics with the same University. He is currently Assistant Lecturer with Department of Pharmaceutics and Pharmaceutical Technology, Bayero University, Kano-Nigeria. He has published 2 papers in reputed journals. He has attended conferences both nationally and internationally, the recent one is the International Pharmaceutical Federation conference held in Dusseldorf, Germany. He is an Exco in a number of associations including Nigerian Association of Pharmacists in Academia (NAPA), Pharmaceutical Society of Nigeria (PSN) and Ahmadu Bello University Alumni Association.
Abstract:
This study is aimed at evaluating the tableting properties of modified starches derived from Plectranthus esculentus as filler/binder by direct compression using metronidazole as a model drug, microcrystalline cellulose (MCC 101) was used as standard for comparison. Fresh tubers of P. esculentus were obtained from Bom area of Plateau state and starch extracted by wet milling. Three modifications of the starch were made, acid hydrolysis (APS), pregelatinization (PPS), and ethanol dehydrated pregelatinization (PPE). For drug-excipient compatibility studies, analytical technique Fourier Transform Infrared Spectroscopy (FTIR) was used. The drug and each of the excipients (1:1 w/w) were thoroughly mixed and analyzed. Powder and tableting properties of these modified starches were evaluated in comparison with microcrystalline cellulose (MCC 101). Powder characterization indicates that modified starches of P. esculentus have better flow properties because they have lower angle of repose (15.65 – 30.050) and higher flow rate (2.85 – 8.25 g/s) in comparison with MCC 101 with an angle of repose of 46.220 and flow rate of 0.80 g/s respectively. The FTIR results revealed no interaction of these excipients with the active drug. APS produced the best metronidazole tablets of better quality in terms crushing strength and friability and also drug-release profile with regards to disintegration and dissolution parameters compared to MCC 101 and other two modifications. Acid hydrolysis of P. esculentus starch therefore produced an excellent directly compressible filler/binder that can be substituted for MCC 101 in conventional tablet formulations.
Peter O’Connell
Trinity College Dublin, Ireland
Title: Modelling chemical and physical stability of cocrystals. Case study: Sulfadimidine: 4-Amino salycilic acid cocrystal
Time : 12:45-13:05
Biography:
Peter O’Connell has completed his BSc in Industrial Chemistry from University of Limerick (Ireland) and MSc in Pharmaceutical Analysis from Trinity College Dublin School of Pharmacy (Ireland) in 2012. Currently, he is involved in a research programme that involves a partnership between Amebis Limited and the School of Pharmacy & Pharmaceutical Sciences at Trinity College Dublin. He has published several papers in reputed journals and has expertise in stability testing, analytical method development, validation and technology transfer for pharmaceuticals.
Abstract:
Salt formation is a common approach to enhance drug solubility but it is not successful when the API does not contain ionisable functional groups in its chemical structure. Engineering of pharmaceutical cocrystals can be an advantageous strategy to overcome poor drug solubility, without the need to break or create covalent bonds. Predicting the shelf life of solid-dose pharmaceutical products using both stressed and accelerated stability data is often desired in order to avoid long development times and costs, associated with real-time stability testing. However, using an accelerated stability programme, stability data gathered over two to four weeks at elevated temperature and humidity conditions can be used to predict stability at lower temperatures. Modelling of physico-chemical stability of cocrystal systems using an accelerated stability program has not been documented. Statistical estimation of both physical and chemical stability parameters is not straightforward due to the non-linearity of modified versions of the Arrhenius equation. Sulfadimidine (SDM) is a poorly-soluble anti-infective agent. In order to improve its aqueous solubility, several cocrystal habits were formed using a GRAS coformer, 4-aminosalycilic acid (4-ASA). Two different polymorphic forms of the cocrystal were prepared containing equimolar ratios of 4-ASA and SDM. The hypothesis underpinning this work is that cocrystal engineering can be used not only to improve the aqueous solubility of the SDM but also its physicochemical stability by changing the cocrystal habit. A four week accelerated stability approach was used to predict the long term physical and chemical stability of different SDM:4-ASA cocrystals with different polymorphic forms and crystal habits.
Fei Cai
Endo International PLC, USA
Title: Advanced technologies in oral delivery: Extrusion spheronization, multiple unit pellet system, sublingual microtablets
Biography:
Fei Cai has developed 20+ drug products in over 8 years of formulation and process development career, among which 4 ANDAs are on the US market. Marketed products include the first-to-market Lamotrigine ER Tablet. Most recently, he had the role of Senior Scientist at Impax Laboratories, and Scientist II at Prinston Pharmaceutical. Prior to Prinston, he was a Scientist of Formulation and Process Development at Patheon where he developed commercial processes for a 505(b)(2) sublingual microtablet. He earned an MA degree in Chemistry from Princeton University. He has 8 publications and invited talks.
Abstract:
Taking one or two pills a day with a glass of water is the easiest and the most acceptable way of administration of a drug to a patient. Various controlled release, solubilization and intraoral delivery technologies have been developed to tailor the drug release profile to meet specific theuraputic needs. A brief overview of various oral and intraoral drug delivery technologies. Controlled release includes taste masking, delayed release, extended relase, multiphasic release, and pulsatile release. Solubilization includes surfactants, particle size reduction, lipid-based systems, and amorphous solid dispersions. Intraoral delivery includes buccal, sublingual, periodontal, lingual, and gingival. Examples of extrusion spheronization, Mutiple Unit Pellet System (MUPS), and sublingual microtablet are presented. Extrusion spheronization has been utilized to produce high drug load spherical substrate for further controlled release coating. Water content, salt level, and wet granules feed rate were found critical of the extrudability and sphere roundness and uniformity for Drug A. MUPS tablets (beads in tablet) offer the benefits of splitable dose and high production rate compared to beads in capsule. However, compaction of pellets is challenging, and beads tend to crack or fuse together and change dissolution profile. Approches of filler particle engineering, and a mixture design of a 3-filler system have been applied to Drug B and C. Sufentanil sublingual microtablet offers the advantage of reducing the amount of swallowed drug. The Zalviso Patient Controlled Analgesia (PCA) system using sufentanil microtablets has been desmontrated superior to current standard of care (IV PCA) in Phase 3 clincical trials.
Flavia Laffleur
University of Innsbruck, Austria
Title: Development of novel mucoadhesive hyaluronic acid derivate as lubricant for the treatment of dry eye syndrome
Time : 16:10-16:30
Biography:
Flavia Laffleur is a Postdoctoral Researcher from University of Innsbruck at the Department of Pharmaceutical Technology.
Abstract:
Dry eye is a disease affecting between 4 and 34% of the population worldwide. Stressful conditions to ocular surface, contact lenses, systemic disease (e.g., antidepressants, thyroid disease and diuretics cause dry eye. Complaints are dryness and tear film instability as well as evaporation caused by ocular surface changes. Therefore, it was aimed to investigate novel synthesized hyaluronic acid derivate evaluating its potential in mucoadhesion and lubricant for the treatment of dry eye syndrome. Hyaluronic acid, a well-known biomaterial in the ocular delivery was chemically modified with cysteine ethyl ester (HA-CYS). HA-CYS was evaluated in terms of mucoadhesive strength on ocular mucosa. Stability measurements and lubricative assay were conducted in form of disintegration and water uptake capacity, respectively. Moreover, safety consideration proceeded with in vitro cell line. Most important Hen's Egg Test on the chorionallantoic membrane for the mucous membrane compatibility was evaluated. According to the results HA-CYS achieved due to this thiolation more pronounced mucoadhesive, stability and lubricative properties enhanced. 3.81-fold increased swelling capacity, 30.5-fold more improved mucoadhesive properties and 9.72-fold higher stability of hyaluronic acid was achieved due to the chemical modification. Thus, the promising results underpin further exploitation of this versatile polysaccharide for treating dry eye syndrome.
Biography:
Associaate Prof. Ahmed Ali has completed his PhD at the age of 33 years from Bradford University School of Pharmacy. He completed his postdoctoral studies at Beni suef University, Faculty of Pharmacy, Egypt. He is now working as associate professor at Faculty of Pharmacy, Taif University, Kingdom Saudia Arabia. He published more than 16 papers in reputed journals and has been serving as a reviewer in many reputed journals such as Journal of pharmaceutical innovation (published by Springer), Journal of drug delivery science and technology (JDDST) and Beni Suef University Journal of Basic and applied Sciences (BUJBAS) published by Elseveir.
Abstract:
The goals of this research were focused on improving the water solubility and dissolution rate of quetiapine fumarate to enable faster oral and buccal bioavailability and enhanced antipsychotic properties. The coamorphous dispersion strategy was achieved using nicotinamide as highly soluble conformer. The prepared quetiapine/ nicotinamide coamorphous dispersions (QNCD) were characterized using scanning electron microscopy (SEM) differential scanning calorimetry (DSC), Fourier transform infra red sepectroscopy (FTIR) and X-ray powder diffraction (XRPD). Static disc intrinisic dissolution rate and ex-vivo diffusion through inverted intestinal tissues were conducted and compared to pure quetiapine. The results demonstrated a highly soluble (QNCD) formed between quetiapine fumarate and nicotinamide at 1:3 molar ratio through H-bonding interactions. The equilibrium solubility results showed 3 folds increase in solubility of quetiapine from the dispersions. High intrinsic dissolution rate (0.603 mg cm-2 min-1) and faster flux rate (0.041 mg cm-2 h-1) were obtained from the dispersion compared to pure quetiapine fumarate (0.284 mg cm-2 min-1) and (0.027 mg cm-2 h-1), repectively. The newly prepared QNCD proved to be effective in improving the drug physicochemical properties and enhanced its ex-vivo diffusion properties. Therefore, this approach could be a considerable solution for new delivery systems of quetiapine by virtue of its augmented physicochemical attributes and improved ex-vivo diffusion which is expected to raise its extra-vascular bioavailability.
- Track 5: Nanotechnology in Drug Delivery Systems
Track 6: Application of Nanotechnology
Location: Melia Avenida America
Chair
Volkmar Weissig
Midwestern University, USA
Co-Chair
Costas Kiparissides
Aristotle University of Thessaloniki, Greece
Session Introduction
Abeer Al-Ghananeem
Sullivan University College of Pharmacy, USA
Title: Pharmaceutical & drug delivery technologies for efficient pain management
Time : 11:25-11:45
Biography:
Professor Al-Ghananeem is the Associate Dean of Research and Graduate Program at Sullivan University College of Pharmacy, Kentucky, USA. She has completed her Ph.D. in Pharmaceutical Sciences from University of Kentucky, USA. Dr. Al-Ghananeem is an author of over 60 peer-reviewed research articles, symposium abstracts, and patent applications. She serves on the Editorial Advisory Board for many reputable pharmaceutical and clinical journals.
Abstract:
Breakthrough pain in cancer patients is a transitory exacerbation of pain experienced for a short period of time by the patient who has relatively stable and adequately controlled baseline pain. Transmucosal drug delivery through intranasal, sublingual, and buccal mucosa are considered an attractive routes to deliver breakthrough pain management medications. It avoids the hepatic first-pass clearance, which results in enhanced bioavailability and faster onset of drug action. The in-vivo pharmacokinetics of three breakthrough pain drugs has been evaluated in rabbis. Conscious rabbits were used, because anesthesia could impair the nasal mucociliary clearance and thereby allowing the formulations to remain in contact with the nasal mucosa for a longer time than would be normally expected without anesthesia. The same apply for the sublingual delivery to mimic the transient time in clinical use. In two separate experiments, the sublingual administration of Fentanyl and Oxycodone showed promising kinetic profiles, resulting in a rapid absorption with acceptable absolute bioavailability up to 82%. Factors such as formulation viscosity and drug moieties of salt versus free base were also evaluated in light of its effect on absolute bioavailability. Furthermore, Tetrahydrocannabenol (THC) intranasal delivery, also showed acceptable bioavailability comparable to the currently marketed soft gelatin capsules formulations, but irritation to nasal mucous membranes requires further drug formulation efforts to overcome this problem. With the increase demand on enhancing the quality of cancer patients’ life, transmucosal delivery offers compelling opportunities to bring new safe and effective drugs to the market.
Costas Kiparissides
Aristotle University of Thessaloniki, Greece
Title: Mucus permeating nanocarriers for the oral delivery of biomolecules
Time : 11:25-11:45
Biography:
Costas Kiparissides is a full time Professor of Chemical Engineering Department (AUTH) since 1981. He was Director of CPERI (2001-2006) and CERTH (2005-2010). He received his diploma in Chemical Engineering from NTUA (1971) and his Ph.D. from McMaster University (1978). He has supervised more than fifty Ph.D. students, 160 diploma theses and has presented more than 300 invited seminars and lectures. He has published 210 papers in refereed journals, 430 conference papers and 24 books and reports. His research interests include advanced multi-scale modeling of chemical and biological systems, functional materials, drug delivery systems, and microbial production of functional biopolymers.
Abstract:
Macromolecular drugs have the unique ability to tackle challenging diseases but their structure, physicochemical properties, stability, pharmacodynamics and pharmacokinetics place stringent demands on the way they are delivered to a specific site/tissue in the body. At present, protein drugs are usually administered parenterally, but this route is less desirable and poses problems of oscillating blood drug concentrations. Moreover, their short biological half-lives necessitate in some cases multiple injections per week causing considerable discomfort to the patients. Nanocarrier based drug delivery systems can diminish the toxicity of biomolecules, improve their bioavailability and make possible their administration via less-invasive routes. To date various types of nanocarriers have been developed for the oral administration of biopharmaceutics. Apart from oral vaccines which target Peyer’s patches that are not covered by a mucus gel layer, nanocarriers have to permeate the mucus gel barrier in order to reach the epithelium. More specifically, an ideal nanocarrier should exhibit an enhanced permeation rate through the mucus gel layer thus allowing the delivery of the therapeutic payload to the epithelium. Additionally, it should exhibit a sustained drug release profile and sufficient protection towards enzymatic degradation of the drug, thus, resulting in increased bioavailability of biomolecules. In this paper, state-of-the-art mucus permeating nanocarriers for controlled delivery of biomolecules are presented and critically assessed (e.g., self-emulsifying drug delivery systems, polyelectrolyte complexes, anionic lipid emulsions, etc.). The nanocarriers were characterized with respect to physicochemical properties, protein loading and release, permeation through fresh porcine intestinal mucus and ability to protect drugs from enzymatic degradation.
Volkmar Weissig
World Mitochondria Society, USA
Title: Mitochondria-targeted nano drug delivery systems
Time : 11:45-12:05
Biography:
Volkmar Weissig, Sc.D., PhD. is a Tenured Full Professor of Pharmacology and Chair of the Department of Pharmaceutical Sciences. Dr. Weissig received his B.S., M.S. and Ph.D. degrees in Chemistry and his postdoctoral Sc.D. degree in Biochemistry and Pharmaceutical Biotechnology from the Martin-Luther University in Halle (Germany). Combined he completed several years of postdoctoral fellowships at the Cardiology Research Center in Moscow (Russia), at the Academic Department of Medicine at the Royal Free Hospital School of Medicine in London (UK), at the Institute of Organic Chemistry at the Czechoslovakian Academy of Science in Prague (CSFR), at the College of Pharmacy and the College of Medicine at the University of Florida, Gainesville, FL and at Harvard Medical School and Massachusetts General Hospital in Boston, MA. Before joining the faculty at Midwestern University, Dr. Weissig was an Assistant Professor of Pharmaceutical Sciences at Northeastern University in Boston, MA. Dr. Weissig holds 16 patents and he has published 98 research papers, review articles and book chapters, mostly in the area of nano drug delivery systems. He also edited and published 8 books. He serves as the Associate Editor of the Journal of Liposome Research and he is member of several other Editorial Boards. In July 2009 Dr. Weissig was inducted into the World Technology Network as a Fellow. In October 2014 Dr. Weissig was elected President of the World Mitochondria Society.
Abstract:
The efficiency and efficacy of drug action depends largely on how well an unaided drug molecule is able to reach its intracellular target or even its target inside organelles such as mitochondria. Subsequently, the specific delivery of a drug to its site of action inside cells will dramatically improve its action. Mitochondria play a key role in apoptosis and several clinically used as well as experimental drugs are known to trigger apoptosis by directly interacting with target site at or inside mitochondria. A random observation at the laboratory bench has helped pave the way towards the development of organelle-targeted pharmaceutical nanocarriers. A fortuitous discovery in the mid-1990s involving the self-assembly of a molecule, known to accumulate inside mitochondria, has led to the development of subcellular nanocarriers suited for the selective delivery of biological active molecules to mitochondria inside living mammalian cells. In this presentation, applications for mitochondria-specific drug and DNA delivery will be described, the current state-of-the-art of mitochondrial drug targeting technology will be reviewed and its future perspective shall be discussed.
Zeeshan Ahmad
De Montfort University, UK
Title: Preparation of novel nano, micro and macro drug delivery systems via Electrohydrodynamic (EHDA) technologies
Time : 12:05-12:25
Biography:
Zeeshan Ahmad obtained his Undergradate Honours and PhD from Queen Mary (University Of London) and Post-Doctoral studies from Queen Mary and University College London (UCL). At present, he is a Reader in Pharmaceutics at The Leicester School of Pharmacy, De Montfrot University, and has published more than 50 peer-reviewed papers in internationally recongised journals. His research has been funded by the UK research councils, the EU and national charities.
Abstract:
The pharmaceutical engineering remit is undergoing rapid changes to accommodate the need for more complex and smaller drug delivery systems. In recent times, several fabrication methods have been developed (e.g., microfluidics, super critical processing, various emulsion systems and even adapted spray drying technologies) to prepare solid nanoparticles (matrix based), solid complex nanoparticles (layered and core-shell encapsulated), flexible vesicles (e.g., lipidic systems) and even fibrous and casted (e.g., patches) drug delivery systems. Electrohydrodynamic (EHDA) Technologies are a rapidly growing set of enabling platforms which permit the controlled (e.g., size and scalability) and ambient condition (e.g., temperature and pressure) engineering of a variety of dosage forms currently of great interest ranging from the nano- up to the macro-scale. This presentation will focus on introducing the underlying concepts of EHDA technologies and how they operate. In addition examples of nanoparticle, complex nanoparticle and micro drug delivery systems will be demonstrated. The use of such materials using various actives will also be highlighted. Finally future potentials of such technologies will be addressed along with current industrial developments in this area.
Serena Mazzucchelli
University of Milan, Italy
Title: Nanometronomic treatment of breast cancer with Doxorubicin loaded H-Ferritin prevents drug resistance and circumvents cardiotoxicity
Time : 12:25-12:45
Biography:
Serena Mazzucchelli, PhD, research associate at the University of Milan (UNIMI). Bachelor degree in Biological Sciences in 2004, degree in Biology in 2006 and PhD in Biological Sciences in 2009 at the Department of Biotechnology and Biosciences (University of Milan-Bicocca-Italy). From 2009 to 2012 she has a post-doc fellowship at the Department of Biomedical and Clinical Sciences “L. Sacco” (UNIMI). Until 2015 she is researcher at the “L. Sacco” University Hospital. Today, SM is carrying out her research focused on the development of nanodevices for diagnosis and therapy of breast cancer at the Department of Biomedical and Clinical Sciences “L. Sacco” (UNIMI). She is an author of more than 20 papers and a reviewer.
Abstract:
Chemotherapeutic treatment of breast cancer is based on maximum tolerated dose (MTD) approach. This strategy, however, presents several disadvantages, including prolonged time intervals between treatment cycles and development of therapeutic resistance. However, advanced stage tumors are not effectively eradicated by MTD owing to suboptimal drug targeting, onset of therapeutic resistance and neoangiogenesis. In contrast, “metronomic” chemotherapy is based on frequent but lower dose drug administrations, resulting in neovascularization inhibition and induction of tumor dormancy.[1] For this reason, metronomic chemotherapy is now envisaged as an interesting alternative for either primary systemic therapy or maintenance therapy. However, low drug accumulation at the tumor and poor effectiveness against highly aggressive metastatic cancer limit the applicability. Here we show the potential of H-ferritin (HFn)-mediated targeted nanodelivery of metronomic doxorubicin (DOX) in the setting of a highly aggressive and metastatic 4T1 breast cancer mouse model with DOX-inducible expression of chemoresistance.We find that HFn-DOX administered at repeated doses of 1.24 mg kg−1 strongly improves the antitumor potential of DOX chemotherapy arresting the tumor progression. We find that such a potent antitumor effect is attributable to multiple nanodrug action beyond cell killing, including inhibition of tumor angiogenesis and controlling the rise of chemoresistance. Multiparametric assessment of heart tissues, including histology, ultrastructural analysis of tissue morphology, and measurement of markers of ROS, provided evidence that metronomic HFn-DOX allowed us to overcome cardiotoxicity. In conclusion, our results suggest that HFn-DOX has potential for the development of novel nanometronomic chemotherapy for the next generation of safe and personalized oncological treatments.
Maria Manuela Gasper
University of Lisbon, Portugal
Title: Paromomycin liposomes - an alternative strategy for treatment of infectious diseases
Time : 12:45-13:05
Biography:
Maria Manuela Gaspar has completed her PhD in 2005 in Pharmaceutical Technology in the University of Lisbon and postdoctoral studies in the University of Dublin, Trinity College. She is a researcher in the Research Institute for Medicines, iMed.Ulisboa, University of Lisbon. The research has been focused on design, development and biological evaluation of drug delivery systems for improving the therapeutic index of incorporated molecules in infectious, inflammatory and cancer animal models. She is co-author of numerous patents, papers in peer-reviewed journals and book chapters.
Abstract:
Infectious diseases constitute an immense global threat, being responsible for 15 million of deaths per year worldwide. Treatment of infectious diseases caused by intracellular microorganisms, such as M. tuberculosis, M. avium, Leishmania and Plasmodium spp. are often hampered by limited access of drugs to infected cells. Over the last decades, liposomes, the most studied and successful drug delivery system allowed to improve the the pharmacologic and therapeutic properties of several molecules. One example is the case of aminoglycosides that due to inappropriate biodistribution and/or pharmacokinetic profiles render them not satisfactory for medical use. Paromomycin (PRM) is an aminoglycoside with a broad spectrum in vitro activity against protozoa and mycobacteria. However, it is poorly absorbed into systemic circulation after oral administration and when parenterally injected undergoes rapid clearance being excreted upon glomerular filtration in urine. In the present work, the association of PRM to liposomes resulted in a huge accumulation of the antibiotic in liver, spleen and lungs, relative to free form. The in vivo biodistribution changes of PRM liposomes were translated into an enhanced therapeutic effect in murine models infected with M. avium and Leishmania infantum with an absence of toxic effects. The obtained results demonstrate the potential of PRM liposomes as an alternative therapeutic strategy for treatment of mycobacterial and parasite infections.
Fabienne Danhier
Louvain Drug research Institute, Belgium
Title: Local delivery of nanomedicines-loaded hydrogel for the treatment of glioblastoma
Time : 13:50-14:10
Biography:
Fabienne Danhier has completed her PhD at the age of 30 years from the Université catholique de Louvain under the supervision of Prof. V. Préat and postdoctoral studies from the INSERM U1066 (Prof. J.P. Benoit), Angers, France. She is currently supervising the group of “nanomedicines for the delivery of anticancer drugs” of the Advanced Drug Delivery and Biomaterials laboratory. She has published more than 25 papers in reputed journals. Two of her papers have been awarded as the first and third papers cited in the 3rd journal in the SJR indicator in pharmaceutical science: Journal of Controlled Release (IF 7.164).
Abstract:
Glioblastoma (GBM) are malignant brain tumors that arise from astrocytes. The annual global incidence of GBM is 6 per 100,000: each year. There is no accepted treatment to prevent recurrences of GBM, in particular from infiltrating cells at the border of resection. Therefore, this clinical situation is considered as an unmet medical need. Two types of hydrogels have been selected to fit the following clinically relevant requirements: injectability, biocompatibility, and very limited cell infiltration. First, polyethylene glycol-based copolymer hydrogels for the delivery of Temozolomide. Second, a specific formulation of lipid nanocapsules that presents adapted rheological properties to directly form a hydrogel for the delivery of Gembictabine. We have shown that hydrogels allow the sustained release of anticancer drugs, are well tolerated in vivo over one week and can significantly reduce the growth of subcutaneous U87MG tumor-bearing nude mice. Thus, these data support the hypothesis that hydrogel could be injected at the resection site and provide a sustained and local delivery of anticancer drugs-loaded nanomedicines that will enable GBM to be treated by maintaining a therapeutic concentration at the resection borders as well as ensuring a sustained diffusion in the surrounding tissue. These approaches provide different perspectives in the development of nanomedicine-loaded hydrogels in relation with the GBM recurrences.
Gary Gellerman
Ariel University, Israel
Title: Novel targeted non-RGD cyclic peptide drug conjugates for treatment of human metastatic melanoma
Time : 14:10-14:30
Biography:
Gary Gellerman has completed his PhD from Tel Aviv University in 1994 and joined Compugen Ltd. In 2000, he accepted VP, Molecular Diversity position in Compugen where he was responsible for developing drug discovery platform. In 2005, he moved to Ariel University, currently holding Deanship of Faculty of Natural Sciences. He has published more than 50 articles in reputed journals.
Abstract:
Metastatic Melanoma (MMel) is the most deadly skin cancer frequently associated with metastasis and poor survival prognosis. Systemic therapy for MMel is still too early in development to demonstrate efficacy, and chemotherapy still remains the major adjuvant treatment against MMel. Obviously, new targeted drug delivery approaches are needed to overcome toxicological problems and improve efficacy. Integrins are a family of at least 24 distinct cell surface receptors commonly over-expressed on many types of cancer cells. They are essential for tumor progression, and therefore attractive targets for selective therapeutic intervention and drug delivery. Importantly, integrins are generally recognized by the “RGD tripeptidic sequence” and therefore many peptides bearing this recognition motif have been found to be effective ligands for the selective delivery of chemotherapeutics. However, their therapeutic and targeted effectiveness was not adequately demonstrated in clinical trials and even paradoxically can enhance, rather than suppress, tumor progression. We developed new non-RGD cyclic peptide ALOS-4 which binds to a non-RGD site on integrin αvβ3. Our preliminary in vivo studies demonstrate that ALOS4 markedly blocks murine B16F10 melanoma tumor growth and lung metastasis, dramatically increases animal survival rates and prevents cancer-related weight loss. In addition, ex vivo fluorescence imaging studies on human metastatic melanoma (WM-266-4) animal model showed the accumulation of the ALOS4-FITC only in the tumor tissue and not in the spleen or liver. The ALOS4-Drug conjugates as well as their potency in treatment of human metastatic melanoma will also be presented.
Yücel Baspinar
Ege University, Turkey
Title: Pitavastatin-containing nanoemulsions: Preparation, characterization and in vitro cytotoxicity
Time : 14:30-14:50
Biography:
Yücel Baspinar received his Ph.D. from Institute of Pharmacy at Free University Berlin 2009 and worked as Post-Doc in the Department Pharmacology & Toxicology until 2010. From 2011-2013 he worked at the Center for Drug Research & Development and Pharmacokinetic Applications (ARGEFAR) as Head of Product Development and Quality Control Laboratory. Since 2013 he is a full time Assistant Professor of Pharmaceutical Biotechnology at the EGE UNIVERSITY, in IZMIR-TURKEY. He has published more than 10 papers in refereed journals. His research interests include Pharmaceutical Nanotechnology, Pharmaceutical Biotechnolgy, drug delivery systems, recombinant DNA technology, drug targeting cancer therapy.
Abstract:
Pitavastatin as a new member of the HMGCoA reductase inhibitors has been designed as a drug with a novel cyclopropyl moiety that resulted in several advantages compared to other statins. PT inhibits the cholesterol synthesis and increased lipoprotein lipase expression at lower doses than other statins. In this study pitavastatin-containing nanoemulsions were prepared in order to increase the intestinal absorption. The effects of the charges of the nanoemulsions and of other physicochemical key properties were studied. The nanoemulsions were produced with a microfluidization method using different homogenization pressures, durations and temperatures. The nanoemulsions were characterized by measuring the droplet size, size distribution, zeta potential and permeability as well as cytotoxicity using Caco-2 cells. Five hundred bar, 15 °C and 3 min were needed for producing positively charged nanoemulsions, while 4 min were needed for preparing negatively charged nanoemulsions. The cytotoxicity studies using Caco-2 cells revealed that both types of nanoemulsions, positively and negatively charged, were not cytotoxic. The positively charged nanoemulsions showed the highest permeation through Caco-2 cell lines, compared to the negatively charged nanoemulsions and a drug solution. The increased permeation of the positively charged nanoemulsion can serve as a sign for a possible increased bioavailability and can probably enhance the absorption of the drug.
Nashiru Billa
University of Nottingham, Malaysia
Title: Food Effects on gastrointestinal transit properties of Amphotericin B solid lipid nanoparticles
Time : 14:50-15:10
Biography:
N Billa completed his PhD in 2000 in the feild of pharmaceutical technology and has since been an academic in various institutions. He is currently a Professor with the School of Pharmacy, University of Nottingham, Malaysia Campus and is also the Associate Dean (Research) at the Faculty of Science. He has supervised over 15 PhD students and published over 30 journal articles
Abstract:
Amphotericin B (AmB) is a polyene antifungal agent highly effective in treating life-threatening systemic fungal infections. We aimed to formulate AmB solid lipid nanoparticles (SLNs) meant for oral delivery and to study the effect of food on the absorption of AmB at the various regions of the gastrointestinal tract using an indirect approach. The indirect estimation utilises paracetamol (PAR) and sulphapyridine (SP) as marker drugs; the SP being a metabolic product of sulphasalazine (SSZ) from the activity of colonic flora. AmB, PAR and SSZ were similarly formulated into SLNs which showed identical physical properties (size, surface charge and morphology) and were simultaneously administered to fasted and fed rats whilst blood samples were withdrawn from their tails simultaneously for HPLC analysis. Cmax was increased by almost twofold and AUC0-30 by more than twofold from AmB SLN compared with AmB suspension however Tmax was increased (0.25 hr vs 4 hr). The presence of food delayed Tmax and significantly (p<0.05) decreased Cmax for the absorption of AmB from the AmB SLN although oral bioavailability (7953 ng.hr/mL vs 7565.33 ng.hr/mL) was not significantly reduced. The plasma concentration-time curves of PAR and SP were used in marking the approximate times at which AmB absorption occurred in the small intestines and colon respectively. The small intestines and the colon showed significant absorption of AmB SLN however, absorption in the colon was considered as partly due to slow drug release into blood from lymphatic drainage in the small intestines. The differences in the estimated percentage absorption of AmB SLNs in the stomach, small and large intestines for both the fasted and fed rats were not statistically significant. We may conclude that improved oral absorption of AmB was achieved following incorporation in SLN and food did not significantly affect the absorption of the AmB SLN from the gastrointestinal tract
B B Barik
Jazan University, KSA
Title: Nanotechnology: A challenge in traditional medicine
Time : 15:10-15:30
Biography:
B B Barik is the Professor in the Department of Pharmaceutics, College of Pharmacy, Jazan University, KSA. He has completed his PhD in 1993 from Jadavpur University, Kolkata, India. Earlier, he worked as Professor and Head in the University Department of Pharmaceutical Sciences, Utkal University, Bhubaneswar, India and College of Pharmaceutical Sciences, Berhampur, Odisha. He has published more than 50 papers in reputed journals and presented more than 100 papers in national and international conferences. He received several awards and medals. He is also serving as Reviewer and Editorial Board Member of reputed journals.
Abstract:
Herbal medicines have been widely used all over the world since ancient times and have been recognized by physicians and patients for their better therapeutic value. The western world has begun to acknowledge the importance of traditional medicines as they symbolize safety in contrast to the allopathic medicines, which tend to produce undesirable side effects and are lacking in curative value. With the advanced nanotechnology, the nanophytomedicines could improve the biological availability and the therapeutic effects, with target-oriented administration, which would adequately improve the therapeutic effects, avoid the adverse effects caused by the long-term drug administration, enhance the quality of life and more importantly explore more prosperous markets for the plant medicines. Nano-phytomedicines are prepared from the active phytoconstituents or standardized extracts. The world market for nanomedicine is estimated to reach $130.9 billion by the fiscal year 2016. It has been widely proposed to combine herbal medicine with nanotechnology. The drug-loaded nanoparticles deliver the herbs (mainly the effective components, regions or the extracts) to the target organ at a sufficient concentration during the entire treatment period. This can accelerate the solubility of the herbs and bioavailability, improve the amphipathic property of the surface of the drug-loaded nanoparticles and permeability, enhance biodistribution and biological effectiveness. Conventional treatments do not meet these requirements. Therefore, integration of the nanocarriers as novel drug delivery systems in the traditional medicine is essential to control more complicated health problems like diabetes, cancer, liver disease, neurological disorders, cardiovascular problems, etc.
Yousef Alomi
Ministry of Health, KSA
Title: New standards and regulations of pharmacy practice in Saudi Arabia
Time : 15:30-15:50
Biography:
Dr. Yousef Alomi, Head of General Administration of Pharmaceutical Care Administration, and Head of National Drug Information Center, MOH Saudi Arabia Dr. Alomi is a product of King Saud University confirmed with the degree of Bachelor of Pharmaceutical Sciences in the year 1992. After six-years of higher study, he earned his Master of Clinical Pharmacy from the same university in the 1998. He is an affiliated clinical instructor of Purdue University in the USA. He is adjunct assistant professor of King Saud University college of Pharmacy. Dr. Alomi worked as clinical pharmacist in critical care area and nutrition support. He is He is establish and implement several programs at MOH Hospitals at first time; Clinical Pharmacy Program, Medication Safety Program, Pain Management Program, Anticoagulation Program and Pharmacy Infection Control, including 30 Adult and 20 Pediatrics Clinical Pharmacy Program; he founder of Mass Gathering Pharmaceutical Care in Saudi Arabia. He became a member of advisory board of the Arab Pharmaceutical Journal in 2010. He became as Pharmacy Board Member of Saudi Commission of Health Care Specialities2010-2013. He had several research papers in clinical Pharmacy and Pharmacy practice published in ACCP and ISPOR conferences; He had several presentations in the clinical pharmacy and pharmacy practice at several conferences in and outside Saudi Arabia.
Abstract:
General Administration of Pharmaceutical Care of Ministry of Health Saudi Arabia is responsible of implementing pharmaceutical care and related issues to 250 hospitals and more than 2500 primary care centers including clinical pharmacy and pharmacy practice programs. It had established strategic planning for pharmaceutical care and setup some standards and new regulation since 2013. Pharmacy human resources of recruitment standard has changed from 0.04 to 0.2 pharmacist per bed, new model of hospital pharmacy design to cover all ASHP standards and regulations, also, clinical pharmacy career pathway specialty starting from general, then specialized and consultant clinical pharmacist and job description for each type and level of pathway had been established. Basic medication safety courses to all medical staff, physicians, pharmacists and nurses should be attended before practicing the job. Applying of national pharmacy practicing system based on international standards with cooperation of Saudi commission of health specialties in Saudi Arabia. In addition to new regulations of pharmacy infection control, mass gathering of pharmaceutical care, and pharmacy R & D in the practice. The pharmaceutical care services is changing tremendously now in quantity and quality to patients car and better diseases management outcome, and avoiding extra and unnecessary cost.
Biography:
Ehsan Shamaeli has completed his PhD from Tarbiat Modares University in Iran. He is pursuing a Post-doctoral program at Tarbiat Modares University conducting research after the completion of his Doctoral studies. He has published 6 papers in reputed journals.
Abstract:
A novel functionalized gold nanoparticle-polypyrrole nanobiocomposite (PPyFGNP-NBC) was fabricated for electrical/pH dual stimuli-responsive local delivery of the hormone insulin. The fabrication method involves simple electrodeposition and immobilization processes without use of organic solvents. Carboxylated GNP, as hydrophilic branches, was used to achieving high loading efficiency for hydrophilic proteins and creating pH-sensitivity. Kinetics analysis showed that release of insulin strongly affected by applying external potential stimuli. Also, the release of insulin was under influence of pH and was slowed down under lower pH. This pH-sensitivity was remarkably increased by applying potential. In vitro release study showed that under applied potential condition, release of insulin in the gastric juice is significantly slower than that in the intestinal fluid. So this smart protein delivery system protects insulin against harmful gastric environment while increases its release in the small intestine. It indicated that the PPy-FGNP-NBC is of potential for use in intelligent oral delivery system. Circular dichroism analysis showed that insulin retained its original conformation during electrochemically-stimulated loading and release.
Mohammed Mehanna
Beirut Arab University, Lebanon
Title: A step towards a safer efficient antituberculosis therapy: Formulation and assessment of Rifampicin targeted inhaled nanocomposite
Time : 16:30-16:50
Biography:
Dr. Mohammed M. Mehanna is an assistant professor at Faculty of Pharmacy, Beirut Arab University, Lebanon. His teaching experience covers different areas of pharmaceutics, pharmaceutical technology, industrial pharmacy and drug delivery systems on both the under- and postgraduate levels. He has published more than twenty papers in international highly ranked journals and conference proceedings both nationally and internationally. He is on the editorial board of several journals including; Journal of Novel Drug Delivery Technology, Journal of Bioavailability and Bioequivalence and International Journal of Pharmacy and Biotechnology. He has participated in the scientific committee of several conferences and serves as a reviewer in a wide range of international journal among them; International Journal of Nanomedicine, Drug development and Industrial Pharmacy, Journal of Pharmaceutical Research, International Journal of Pharmaceutics, and Journal of Pharmaceutical Sciences. He is supervising several master and Ph.D. theses in both Lebanon and Egypt. His research interest is pharmaceutical nanotechnology and non-invasive drug delivery systems with a particular emphasis on tailoring liposomes and nanocarriers for various drugs especially anticancer through different routes of administration.
Abstract:
Rifampicin, despite of being the most effective antitubercular drug; its efficacy encounter obstacles mainly; poor bioavailability and therapeutic activity is concentration-dependent. Nanocrystals, a new carrier-free colloidal drug delivery system, is thought as a viable drug delivery strategy to develop the poorly soluble drugs. Rifampicin nanosuspensions were fabricated using the anti-solvent precipitation technique. The impact of solvent type and flow rate, stabilizer type and concentration, stirring time and apparatus together with the solvent-antisolvent volume ratios on this controlled nanocrystallization have been evaluated. Nanocrystals were characterized by TEM, particle size and zeta potential analysis, solubility and dissolution profiles. The compatibility between RIF and the stabilizer were investigated via FTIR and the DSC techniques. The shelf-life stability of the optimized nanosuspension was assessed within a period of three months at different storage temperatures. Cell cytotoxicity was evaluated using MTT assay on lung epithelial cells. In addition, design of an inhaled targeted nanocomposite based carbohydrate was performed and their aerosolization performance was assessed. The results obtained highlighted that polyvinyl alcohol at 0.4% w/v, 1:15 methanol to deionized water volume ratio and 30 min sonication were the optimal parameters for RIF NS preparation. Nanocrystals were obtained with a particle size (101 nm) and zeta potential (-26mV) additionally, exhibited 50 folds enhancement in rifampicin solubility and 97% of RIF was dissolved after 10 minutes. The prepared nanosuspension was stable at 4±0.5 °C with no significant change in particle size or zeta potential. The MTT cytotoxicity assay of rifampicin nanosuspension demonstrated a good safety profile, reduction in cell cytotoxicity with IC50 values of 0.5 and 0.8 mg/mL for rifampicin powder and optimized nanocrystals, respectively. With aid of some carbohydrates, nanocrystals were transformed into decorated microparticles, which is suitable for inhalation therapy. The formulated nanocomposite was able to deliver the drug to the infected alveoli. Novel rifampicin-loaded nanocomposite could be followed as an approach for enhancing rifampicin therapeutic outcomes which initiating the generation of a wave for an efficient strategy for safe targeted delivery of such a poorly soluble drug to the lung.
Jin Xie
The University of Georgia, USA
Title: Surface modified ferritin nanoparticles for imaging and drug delivery
Biography:
Dr. Jin Xie received PhD in chemistry from Brown University in 2008. He then did two postdocs at Stanford Medical School and National Insitutes of Health, respectively. In 2011, he joined the faculty of the University of Georgia and started his own research program. He has published 65 research articles
Abstract:
Ferritins are a family of iron storage proteins with ubiquitous distribution among almost all life forms. Ferritins feature a cage-like structure, with an outer diameter of approximately 12 nm and an inner cavity of 7−8 nm. While natural ferritins are always filled with a ferric oxohydroxy core, artificially made ferritins have an empty cavity at the center. Ferritins are decomposed into the 24 subunits when the pH is decreased to 2~3; when the pH is tuned back to neutral, however, the subunits can reconstitute into a nanocage, and in a nearly intact fashion. Such pH-mediated disassembly-and-reassembly provides a facile means to load molecules into ferritins. For instance, we recently reported that chemotherapeutics like doxorubicin can be into ferritins with high efficiency. Moreover, we found that ZnF16Pc, a potent photosensitizer, can be loaded into ferritins by up to 60wt%. Meanwhile, the surface of ferritins can be modified, through either chemical conjugation or genetic engineering, to present tumor targeting ligands. These features of ferritins, along with their intrinsic biocompatibility and biodegradability, suggest great potential of the platform as a novel delivery system. More recently, we found that ZnF16Pc-loaded and RGD4C presenting ferritins can home to tumor endothelium; with photo-irradiation at relatively low fluences, the resulting PDT treatment leads permeabilized tumor vasculatures. As a result, macromolecules or nanoparticles administered afterwards are able to extravasate and accumulate more efficiently at the tumor sites. This methodology can artificially enhance the EPR effect of tumors so as to improve nanoparticle delivery to tumors
Behruz Barfi
Samen Pharmaceutical Company, Iran
Title: Nanomaterials-A distinctive but endless world in drug delivery systems
Biography:
Behruz Barfi has completed his PhD at the age of 34 years from Semnan University. He has published more than 22 papers in reputed journals and has been serving as an editorial board member of repute.
Abstract:
There are numerous challenges that the drug alone finds hard to overcome, such as the attack of enzymes, the poor permeability of some tissues, and the difficulty of access to the target once arriving at the destination cells, among others. As a consequence, the treatments usually involve the administration of relatively high doses of drug with the hope that a portion, although minor, goes to the right tissues or cells. The situation becomes worse in the case of new active substances obtained via biotechnological processes (peptides, enzymes, genes etc.), which have a complex structure and too deficient physicochemical and stability features to be able to reach/withstand the blood circulation. The ability to use nanotechnology to alter the characteristics of a drug to increase solubility, decrease degradation during circulation, and concentrate the drug at the desired site of action promises to increase efficacy while decreasing unwanted side effects. The development of an effective, versatile delivery option in nano-scale for the targeted delivery of therapeutic compounds has the potential to radically improve disease outcomes. The enormity of this opportunity has spurred much funding and research aimed toward the development of various nanoparticles for drug delivery systems. Herein, we will attempt to give insights into the currently developed drug delivery systems based on nano-sacales and present the resulting findings in an innovative manner, showing nanomaterials make a distinctive but endless world in the drug delivery systems.
- Track 3: Recent Advances in Drug Delivery Technology
Track 7: Major Challenges in Drug Delivery System
Track 11: Medical Devices for Drug Delivery
Location: Melia Avenida America
Chair
Amiram Goldblum
The Hebrew University of Jerusalem, Israel
Co-Chair
B B Barik
Jazan University, KSA
Session Introduction
Paul Fisher
Inovio Pharmaceuticals Inc, USA
Title: Enhanced delivery of DNA-based vaccines and immunotherapeutics through next-generation electroporation devices
Time : 09:55-10:15
Biography:
Paul Fisher is a Bioengineering Scientist at Inovio Pharmaceuticals, where he is investigating the delivery of DNA-based therapeutics. He received his B.S. in Biomedical Engineering from the University of California, Irvine, and his Ph.D. in Biomedical Engineering from the University of Kentucky. Dr. Fisher has a background in controlled drug release from implantable and injectable biomaterials, with a focus on regenerative medicine. He has two patents pending for his work on novel sustained drug delivery systems using biodegradable polymers.
Abstract:
It is well known that naked DNA vaccination alone is insufficient to generate clinically relevant immune responses due to inefficient cellular uptake. In vivo electroporation (EP) has been shown as an efficient non-viral method for enhancing DNA vaccine delivery and immunogenicity in animals and humans over the past twenty years. In a recent randomized, double-blind, placebo-controlled phase 2b study, Inovio Pharmaceuticals has successfully demonstrated therapeutic vaccination of CIN2/3 patients with VGX-3100, a highly optimized HPV-16/18 DNA vaccine, administered by CELLECTRA® EP device resulted in robust cellular and humoral immune responses, significant viral clearance and, importantly, significant regression to CIN1 or no disease. Inovio is currently developing additional EP devices for DNA delivery to a variety of tissues, such as muscle and skin. One of the examples- Surface Electroporation Device (SEP), which only contacts the surface of the skin and does not penetrate the skin, is capable of efficient delivery of DNA vaccines into the skin while establishing that these parameters are sufficient to elicit both robust and sustainable humoral as well as cellular immune responses without tissue damage. Here we will discuss the impact of these devices on in vivo DNA uptake and how different EP strategies can be used to optimize delivery of DNA-based vaccines and immunotherapeutics for a variety of therapeutic indications for different applications.
Catarina Duarte
IBET, Portugal
Title: Application of high pressure technology for the development of intranasal delivery systems
Time : 10:15-10:35
Biography:
Dr. Catarina Duarte has a PhD in Physical-Chemistry (1997, Universidade Nova de Lisboa). She is the head of the Nutraceuticals and Delivery Group of IBET,Portugal (since2003), coordinator of R&D activities and responsible for technology transfer between academia and industry. Research interests include the development of clean technologies for the development of new functional formulations, with application in pharmaceutical, cosmetic or food industries. Regularly provides support for innovation, research and development of new products. She is author of 88 accepted papers in peer-reviewed scientific periodicals, several book chapters and communications in international meetings.
Abstract:
Intranasal route have emerged in last years as an effective approach, even to brain delivery of drugs, as the brain and nose compartments are connected to each other via the olfactory/trigeminal systems. With this purposes, biocompatible drug delivery systems (DDS) including polymer-based or lipid-based systems have been studied and many formulations developed. In the present, new DDS such as multilayered microspheres and hybrid [polymer-lipid] dry forms are considered as alternative. This presentation will focus on the application of high pressure processes (e.g. supercritical fluid technology) as an alternative to conventional precipitation processes, and a precipitation technique that avoids completely the use of organic solvents will be presented. As exemples, the results on two hybrid delivery systems: [Gelucire 43/01™:PEG 4000] and [Gelucire 43/01™:GMO], produced by the PGSS® method(Particles from Gas Saturated Solutions) will be shown. Moreover, alginate-based hybrid aerogels (with low methoxyl pectin and κ-carrageenan), in the form of microparticles dried with supercritical CO2, will be presented as carriers for mucosal administration of drugs. These DDS were designed to allow the improved absorption of low molecular weight drugs or peptides after their administration though nasal mucosal tissue.
Gavin Walker
University of Limerick, Ireland
Title: Bioactive PCL matrices with a range of structural & rheological properties
Time : 11:05-11:25
Biography:
Since 2012, Professor Gavin Walker has been awarded >€20,000,000 as Principal Investigator, specifically contributing to advanced in Chemical Engineering on 15 projects from EU (H2020, FP7, Marie-Curie), UK government (TSB, EPSRC) Irish Government (SFI, EI), UK Charities and Industrial sources. Prof. Walker is PI on Pharmaceutical Manufacturing Technology Centre (PMTC); PI on EI Dairy Processing Technology Centre (DPTC); Synthesis and Solid State Pharmaceutical Centre (SSPC) at the University of Limerick.
Abstract:
Safer pharmaceutical and medical devices excipient are being sought as alternatives to polyvinyl polymers that are commonly plasticised by carcinogenic phthalates. This paper demonstrates a biodegradable and non-toxic bioactive polymer matrix whose structural and rheological properties can be easily modified by the amount of added plasticiser, while being only mildly affected by the presence of a low dosage API. Poly(ε–caprolactone) (PCL) was selected as an alternative polymer to polyvinyls as it is biodegradable and has high amorphous content, which improves drug solubility. Bulk PCL and various blends with 5 and 25% polyethylene glycol (PEG, a plasticiser and pore former) and 5% nalidixic acid (NA, the bioactive) were processed using extrusion and pressed into plaques. The resultant material properties were investigated in terms of microscopic, morphological and topographical modification. No evidence of miscibility was found by IR. The rheology and contact angle of the matrix could be easily manipulated through the addition of PEG. An increased loading of PEG to 25% (w/w) caused a 10 fold increase in the melt flow index, a similar increase in the elongational viscosity, and a contact angle decrease of 10°, indicating that the resultant fluid was becoming more Newtonian. It was concluded that the structural and rheological properties of the blend, while easily modified through the addition of PEG, were unaffected by the monodispersion of the API, nalidixic acid.
Luisa Fiandra
University of Milan, Italy
Title: Targeted inorganic nanodevices for breast cancer diagnosis and therapy
Time : 10:35-10:55
Biography:
Luisa Fiandra has completed his PhD and postdoctoral studies from the Department of Biology of the University of Milan (Unimi), working in the field of transport physiology with a specific interest in permeability processes through intact epithelia and cell membranes. From 2010 to 2015 LF has been senior researcher at L. Sacco Hospital (Milan), where she contributed establish the Nanomedicine Unit, and scientific coordinator of the NanoMeDia Project, funded by Regione Lombardia (Italy). Today, LF is carrying out her research activity, mainly focused on the breast cancer targeting and therapy by nanoformulated drugs, and on the delivery of antiretrovirals across biological barriers, at the Department of Biomedical and Clinical Sciences “L. Sacco” of Unimi.
Abstract:
Among the various kinds of tumors, breast cancer represents a target of primary interest, both from a diagnostic and a therapeutic point of view. In this context, powerful target-specific magnetic nanodevices can represent efficient contrast agent for MRI detection and good delivery system for anticancer drugs. Nowadays, many efforts are devoted to design nanosystems which can be localized at cancer cells for an extended period of time, in order to optimize diagnostic sensitivity and therapeutic efficiency. A valid example is represented by a versatile molecular superparamagnetic nanocomplex, functionalized with the commercial anti-human epidermal growth factor receptor 2 (HER2) trastuzumab (TZ) or TZ-derivatives. Several in vitro and in vivo experiments demonstrated the dependence of HER2 targeting efficiency from the structural features of the immobilized homing ligands. Moreover, the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting and therapeutic effect was demonstrated. The best in vivo activity was obtained with monofunctionalized Tz- as compared with bifunctionalized Tz-nanoparticles.
Havazelet Bianco-Peled
Technion–Israel Institute of Technology, Israel
Title: Composite hydrogels: An innovative approach for controlled release of hydrophobic drugs
Time : 11:10-11:30
Biography:
Havazelet Bianco-Peled is a Professor of Chemical of Engineering since 1999. She has received several awards for her professional accomplishments. She has written more than 70 research publications in reputed journals, edited a book, and has ten patent applications either granted or pending. She is the Founder and CSO of SEAlantis Ltd., a company that develops, manufactures and commercialize novel biomimetic tissue adhesives base on a technology invented in her lab.
Abstract:
Many of the new medical entities are extremely hydrophobic. These drugs offer advantages such as better targeting and efficiency. However, their low water solubility is related with low bioavailability and risk of aggregation upon intravenous administration. We present an innovative methodology for sustained delivery of hydrophobic drugs using composite hydrogels, prepared by embedding oil-in-water microemulsions in hydrophilic hydrogels. Creating composite hydrogels increases drug loading due to its higher solubility in the oil droplets, while the crosslinked hydrogel matrix could be readily used as a solid controlled delivery vehicle. We formulated alginate and chitosan composite hydrogels from pharmaceutical accepted components. The oil droplets diameter was shown to be 10 nm by dynamic light scattering, cryo-TEM and SAXS. All hydrogels were capable of loading hydrophobic compounds with a wide range of logP. The gels were clear with no precipitations, indicating the solubility of the drugs in the gels. Release profiles from hydrogels with various concentrations of polymer and crosslinker demonstrate the applicability of this system as a controlled delivery vehicle, and suggest that the release rate is governed by the network properties. The release from alginate composite hydrogels was similar for different microemulsion formulations, various drugs and increasing concentrations of a drug. These findings indicate that these hydrogels could potentially act as a generic system, where the properties of the release do not depend on the drug but rather on the attributes of the gel. The release mechanism from chitosan hydrogels was more complex due to polymer–microemulasion interactions.
Abdelazim Zaghloul
Kuwait University, Kuwait
Title: Preparation and in-vitro/in-vivo evaluation of metformin hydrochloride rectal dosage form
Time : 11:30-11:50
Biography:
Dr. Abdelazim Zaghloul is an Associate Professor of Pharmaceutics at Faculty of Pharmacy, Kuwait University. He earned his BSC of Pharmacy fromAlexandria University and his MSc and PhD Degrees in Pharmaceutics from Al-Azhar University, Egypt. From1999-2003, he worked as a Postdoctoral Research Fellow at School of Pharmacy, Texas Tech University. Dr. Zaghloul has published more than 30 articles in per-reviewed international journals and presented more than 50 podium and poster presentations to national and international meetings. Dr. Zaghloul main research interest focus on drug delivery, design and development of various dosage forms, physicochemical characterization and evaluation of critical process and formulation variables by optimization procedures and neural networks.
Abstract:
Metformin hydrochloride (MtHcl) is an oral antidiabetic drug and has been used successfully to treat polycystic ovary and overweight patients. However, the available commercial dosage form is the oral tablets that has poor bioavailability, narrow absorption window and extensive first pass metabolizm in the liver. The aim of this work was to formulate MtHcl as a rectal suppository dosage form to partially bypass the liver metabolism, improve the absorption and bioavailability and to be a good alternative for children and elders who cannot take the oral tablets. For this purpose , suppository fatty bases (Witepsol®, Suppocire® and Massa®; different grades) and PEG bases 1000, 4000 and 6000 (different ratios), were used to prepare rectal suppositories each containing 500 mg drug by fusion method. The formulations were characterized for mechanical strength, melting time, penetration time, content uniformity, and in-vitro drug release. Based on the results, three formulations containing Witepsol H12 (F1), Suppocire AP (F2) and Massa Estranium B (F3) were chosen for bioavailability testing in human volunteers using the commercial oral tablets (500mg) as a reference (Ref). The results indicated that the preparation method applied produced suppositories with satisfactory characteristics. The fatty bases were superior compared with PEG bases. The average melting time for F1-F3 was 8 min, the drug content uniformity ranged between 95-105%, the mechanical strength ranged between 7-8kg/cm, the penetration time ranged between 6-8 min and the in-vitro drug release was more than 90% in the first hour of dissolution time. The in-vivo results were: Tmax 0.25, 0.5, 0.25, 3 hr; C max 7254.11, 8319.19, 8423.36, 1125.01 ug/ml for F1, F2, F3 and Ref, respectively The % relative bioavailability for F1, F2, F3 against the Ref. were 76.65, 100.95 and 99.01 respectively. In conclusion, the results indicated that MtHcl rectal suppositories were successfully prepared and characterized and the fatty bases showed better characteristics compared with the PEG bases. F2 and F3 showed comparable bioavailability with the commercial tablets. MtHcl formulated in fatty bases could be a potential alternative to the commercial tablets particularly for pediatric and geriatric patients.
Biography:
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Abstract:
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Dimitris Hatziavramidis
National Technical University of Athens, Greece
Title: A posterior-eye drug delivery system for treatment of age-related macular degeneration
Biography:
Dimitris Hatziavramidis has completed his BSc at NTUA (Greece), his MSc at University of Manchester (UK) and his PhD at University of Illinois (USA). He has spent most part of his career working for academic institutions and large corporations in the USA and is currently a professor at NTUA. Prior to this, he served as a professor and Director of the Particle Technology and Crystallization Center for pharmaceutical products, in the Department of Biological and Chemical Engineering at Illinois Institute of Technology in Chicago, IL. He is a Fellow of AIChE. He has published extensively in reputed journals and has several patents.
Abstract:
Age-related macular degeneration (AMD) is a progressive, neurodegenerative, occular disease and a leading cause of irreversible loss of vision in aging adults in developed countries. Its pathogenesis is characterized by uncontrolled proliferation of cells and cell growth in blood vessels, leaking of blood and proteins and aberrant folding, aggregation and accumulation of proteins. Overexpression of the vascular epithelial growth factor (VEGF) causes uncontrolled blood vessel growth resulting in violation of the blood-retina barrier and accumulation of blood and protein debris causes neurodegeneration of cells in the retinal pigmented epithelium (RPE) and tissue disfunction. The current treatment of AMD is primarily based on anti-VEGF drugs which are administered by intravitreal injection. It has been recently proposed to administer exogenous Heat shock proteins such as Hsp70 by intravitreal injection in order to clear accumulated debris from RPE and inhibit aggregate-based cell neurodegeneration. An equally effective and less vision-threatening than intravitreal injection route of administration of the above macromolecular drugs is transscleral delivery from an implant in the posterior eye, thermally-sensitive A study for sustained delivery of an anti-VEGF agent to the posterior eye from an implant, made of a poly(N-isopropylacrylamide) (NIPAM) thermally sensitive gel. This gel undergoes a phase transition characterized by a lower critical solution temperature (LCST) of 33oC, below which the drug is loaded in the gel and above which the drug is released from the gel.
Amiram Goldblum
The Hebrew University of Jerusalem, Israel
Title: Computer-aided design of liposomal drugs: In silico prediction and experimental validation of drug candidates
Biography:
Amiram Goldblum is the Head of the Molecular Modeling and Drug Design and Discovery Unit at the Institute for Drug Research of the Hebrew University. Following a BSc in Chemistry and Physics and a MSc in QM studies of molecular spectra, his PhD is in Organic Reaction Mechanisms (Mechoulam, Hebrew U). He completed his Post-doctoral studies of Quantum Biochemistry (Paris), QSAR and QM reaction mechanisms (California). He receieved his first award at the American Chemical Society National Meeting in Washington DC 2000 for his algorithm called "Iterative Stochastic Elimination" (ISE) used to solve extremely complex combinatorial problems and focuses in recent years on Molecular Discovery by Chemoinformatics.
Abstract:
Liposomes are the most extensively clinically used drug delivery system. Since the FDA approval of the first nano-drug Doxil®, more than 12 other liposomal drugs were approved by the FDA and more liposomal drugs are under development. Doxil is based on the combination of high and stable drug loading which is also responsible for the controlled drug release as well as on the use of nano-pegylated liposomes. Pegylated nano-liposomes are important for treating cancers, neurodegenerative and inflammatory disorders, as they take advantage of the enhanced permeability and retention (EPR) effect and deliver drugs to the site of disease. Development of liposomal formulations is a time consuming process which requires major efforts. A more rational and less labor intense process is, taking advantage of computational modeling approaches capable of predicting whether an active pharmaceutical ingredient (API) could be loaded to and delivered by liposomes. Towards that end, Quantitative Structure– Property Relationship (QSPR) models were developed with iterative stochastic elimination and k-nearest neighbors approaches to predict drug loading efficiency (high vs. low) in liposomes. Chemical as well as formulation descriptors were employed and the resulting statistically validated models were used to screen a few thousand biologically active molecules from the Comprehensive Medicinal Chemistry database. Three drugs were selected for experimental testing of their loading into nano-liposomes, also taking into account challenges of nano-liposomal development. Two of the selected drugs were high-and one was low-loading, confirming the predictions. Ten other negative molecules from literature were also confirmed, to a total prediction accuracy of 92%. Screening results of CMC database were obtained by the two computational approaches (ISE and kNN). One of the tested drugs- mupirocin, was remotely loaded into pegylated nano-liposomes, and stabilized by intraliposomal hydroxypropyl-β-cyclodextrin to form nano-mupirocin, which was evaluated in vivo for its therapeutic efficacy. Mupirocin, an antibiotic with a unique mode of action is currently restricted to topical administration due to its rapid degradation in the blood. Intravenous administration of nano-mupiricin to mice in necrotizing fasciitis model showed significant superiority of nano-mupirocin over mupirocin. Our approach demonstrates the utility of QSPR models in screening API libraries for identifying candidates that should benefit from being administered as nano-drugs.
Prashant Shalikram Khemariya
SRK Pharmaceuticals, India
Title: An approach and big hope from “Mosquito Eradicator Statue†to make India as mosquito free India
Biography:
Prashant Shalikram Khemariya is a well known young scientist of India. His expertises are in the field of Pharmaceutical and Biotech Products Development. Now days he is based in Malaysia and working with one of the leading Pharmaceutical Company in Research and development. He has more than 15 international and National research/ review publications and few are under process. For last 6 years he has been on the journey of research. He has successfully developed more than 80 ANDA products and worked with NDA Molecules. In wound and cancer Management Prashant Shalikram Khemariya is very enthusiastic.
Abstract:
According to WHO- International and domestic funding for malaria control and elimination was approx US$ 2.7 billion in 2013, even after that 3.2 billion people, almost half of the world’s population are at risk of malaria. Not only were that till September 2015, there 214 million cases of malaria and 438,000 deaths. As per American Mosquito Control Association (AMCA) there are approx 3000 varieties of mosquitoes and Culex, Anopheles, and Aedes genera are the most common and most dangerous responsible to Malaria and Dengue fever. 120000 mosquitoes would be enough to completely drain out the blood of average human just within 3 minutes of short time. So no wonder to say that mosquitoes have been described as the “world’s deadliest animalâ€. Mosquito likes dark colors (most favorite black) and O+ blood is very delicious for them, resulting people with O+ blood group are always on mosquito’s demands. Actually, only the female mosquitoes bite people, but not for her meal, although they are searching Isoleucine in human blood that is one of the basic building blocks of life. Human blood is not the best source for Isoleucine, blood from buffaloes and rats contains more Isoleucine, but since people outnumber rats and buffaloes in many places the mosquitoes bite us instead. Female mosquito may lay as 200-300 eggs if she has Isoleucine otherwise only 10. Female Anopheles Gambiae is one of the best known for a predominant role in the transmission of the most dangerous malaria parasite species called Plasmodium falciparum. Female mosquitoes have nerve cells called cpA neurons that have a receptor to detect carbon dioxide and chemicals secreted through human skin. An average person’s respirations generate approximately 450 liters of carbon dioxide, 1500 mmols of lactate and expel few chemicals from the skin per day, by thee smell of these chemicals mosquitoes tracks our location. The aim of presenting research is to make a hollow statue containing few thin layers of soft gelatin (tensile strength 15-20 MPa) and that will be reacting as a Human body. The outer layer will be dark black with 1.5-2.5 mm of thickness and have “Chemical A†( containing L-Lactic Acid, ammonia, carboxylic acids, Carbon Dioxide and octenol in a particular combination) and an inner layer will be approx 2-3 micron of thickness, 12-20% of moisture and overlap with a W/O emulsion of a Carbamate. Outer layer of the statue will release “Chemical A†(containing CO2 and other chemicals) in mist form, this chemical will be enough to attract female mosquitoes. To drill outer layer of the statue a female mosquito will need 15-17 Hz, pressure and a vibratory cutting frequency of 200-400 Hz by her fascicle with 1.8mm length and 11.0 mm internal radius, now condition will be same as epidermis (outer layer of human skin). When mosquito will sit on outer layer and drill it, fascicle reaches to an inner layer of statue that having Carbamate in liquid form and she will suck it. Carbamate actually affect the activity of acetylcholinestearase (AChE), which is responsible for the hydrolysis of acetylcholine (ACh), it is a neurotransmitter. This chemical act as synapses in the Central Nervous System of the mosquito. Following the inhibition of AChE caused by carbamylation, ACh will accumulate thus prolonging the action of the Neurotransmitter at the cholinergic synapses, resulting hyper excitation of the CNS will accompanied by convulsion, then paralysis and ultimately it will lead to the death of the mosquito. One State will be enough for 2.80 Sq acres are and few more statues will make entire city free from Mosquitoes.
- Lunch Break
Location: Melia Avenida America
- Track 12: Smart Drug Delivery Systems
Track 13: Delivery Methods for Peptides and Biologics
Location: Melia Avenida America
Chair
Drazen Raucher
University of Mississippi Medical Center, USA
Co-Chair
Kang Choon Lee
SungKyunKwan University, Republic of South Korea
Biography:
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Abstract:
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Biography:
J Richard has got a PhD in Materials Science (University of Paris VI, 1987). He is Senior Vice President for Peptides Development in Ipsen. He has published 67 peer-reviewed scientific papers, 8 book chapters and 2 review editorials in various fields (colloids and interfaces, drug delivery, supercritical fluids, protein formulations, nanoparticles, sustained-release formulations . . .). He is the author of more than 120 international communications and 53 patent families.
Abstract:
Due to their physicochemical characteristics, peptides are usually administered through the parenteral route, often several times daily. Injectable sustained-release peptide formulations based on biodegradable microparticles or implants have been very successful to enhance patient adherence and convenience, and increase safety and efficacy. They are likely to remain a significant and important part of the new peptide products coming to the market. However, the tremendous developments in alternative non-invasive routes of delivery are likely to result in more and more peptides being delivered by the transdermal, nasal, inhalation and oral routes. The main purpose of this talk will be to analyze and compare the various oral peptide delivery technologies progressing in the clinic, discussing the pros and cons of these technologies in regards to stability, bioavailability, safety/efficacy balance, impact on CoGs and manufacturability. Case studies will be presented and discussed, examining clinical results and models for oral peptides in development addressing the key points: - Will the oral bioavailability of peptides be sufficient to fulfill the requirements of health economics and safety? - How the oral pharmacokinetics and efficacy compare versus subcutaneous injection? - Can oral peptide delivery technologies overcome food effects?
Kang Choon Lee
SungKyunKwan University, South Korea
Title: Smart high molecular PEGylated exendin-4 as a noble long-acting type 2 diabetic therapy
Biography:
Dr. Kang Choon Lee is Haengdan Distinguished Professor at School of Pharmacy, SungKyunKwan University, Korea. For over 35 years, Dr. Lee’s Drug Targeting Laboratory has been focused on immuno-targeting and bioconjugation of peptide and protein drugs. Dr. Lee is internationally recognized as one of the leading experts in site-specific peptide/protein PEGylation and firstly demonstrated the therapeutic potential of novel site-specific PEGylated drugs such as GLP-1 and TRAIL. He has published over 150 papers in peer-reviewed journals and served as an invited speaker at many international conferences. Dr. Lee is an inventor on more than 20 patents related to specific bioconjugation and PEGylation of peptide/protein drugs. Dr. Lee is honored as a Fellow of the American Association of Pharmaceutical Scientists (AAPS) in 2003. He currently serves on the editorial advisory board of many international scientific journals.
Abstract:
Exendin-4, a GLP-1 receptor agonists is viewed as potent therapeutic peptide for type 2 diabetes. Yet due to the short circulating half-life, high doses of the drug must be administered frequently which gives rise to concentration-dependent adverse effects. The high molecular PEGylated Exendin-4 was created by site specifically attaching a novel polyethylene glycol (PEG) molecule to Exendin-4. The PK in rats, dogs and monkeys and the PD in diabetic mice models are compared. Unlike existing PEGylation technology or other half-life extension technologies that often significantly reduce the biological activities of peptide drugs, modification of Exendin-4 with smart PEGylation approach enables a very long biological half-life (t1/2: 88 hr in cynomolgus monkeys) combined with retention of Exendin-4’s potency, resulting in a long duration of action with potentially reduced adverse effects in humans. In turn, this can lead to weekly and monthly dosing frequencies with low adverse effects and overall provide higher patient compliance.
Drazen Raucher
University of Mississippi Medical Center, USA
Title: Thermally targeted delivery of anticancer therapeutic peptides using elastin-like biopolymers
Time : 13:50-14:10
Biography:
Drazen Raucher received his PhD (1995) in Molecular Biophysics from the Institute of Molecular Biophysics at Florida State University. He then pursued postdoctoral studies in Cell Biology and Biomedical Engineering at Duke University, USA. He is currently a Professor of Biochemistry at the University of Mississippi Medical Center. He pioneered the use of cell penetrating elastin-like peptides for the delivery of therapeutic peptides that modulate the activity of aberrant molecular pathways in cancer. His research interests include thermally targeted biopolymer drug carriers and drug-delivery systems in oncology. He has published more than 50 articles and is co-author of two patents.
Abstract:
Current cancer therapy is limited by severe toxicity from systemic administration of antineoplastic agents. Motivated by limitations to current therapeutic approaches for cancer, we developed an externally triggered drug delivery system with the potential to selectively deliver anti-cancer drugs to tumors, increase therapeutic specificity and efficacy, and reduce cytotoxicity to normal tissues. This drug delivery system consists of a thermally responsive polypeptide whose amino acid sequence is based on elastin-like polypeptide (ELP) biopolymers. The polypeptides are genetically engineered, allowing incorporation of a therapeutic peptide sequence in the ELP carrier by simple molecular biology. ELP is further modified by adding cell penetrating peptides (CPPs), which allow targeting of therapeutic peptides to different tissues or intracellular compartments and also enables crossing of the blood-brain barrier. The conjugation of the ELP delivery system with therapeutic peptides targeting cell cycle, oncogenic, and apoptotic pathways has resulted in enhanced cellular uptake rates, increased apoptosis, and cancer cell killing. The clinical potential of the ELP delivery system was confirmed in animal tumor models that demonstrated hyperthermia-induced aggregation of ELPs due to phase transition of these polypeptides, providing a new way to thermally target ELP therapeutic peptides conjugates to solid tumors. This drug delivery system has the potential to provide a method for targeted delivery of chemotherapeutic agents to tumor cells. The system exploits clinically available applications of external hyperthermia to induce site-specific drug carrier accumulation of anti-cancer drugs through a technology that is both easy to implement and feasible for a broad range of cancer types.
Noel M Elman
Massachusetts Institute of Technology, USA
Title: Rapid reconstitution packages (rrps) for emergency delivery of glucagon: Hypoglycemia treatment in type 1 diabetes (T1D)
Time : 10:55-11:15
Biography:
Noel Elman is currently a research scientist and principal investigator at the Institute for Soldier Nanotechnologies at the Massachusetts Institute of Technology (MIT). His research translational research group is focused on development of biomedical devices for therapeutics and diagnostics, as well as investigation of novel biotechnological platforms. Noel is also the founder of high-tech startups in the field of micro devices, and is authored of over 30 scientific papers, chapters and books.
Abstract:
Hypoglycemia is a condition characterized by abnormally low blood glucose (e.g., blood sugar) levels. Glucagon is an effective therapy for severe hypoglycemia however it is reported to be unstable in liquid form. Therefore, smart technological platforms must be engineering to keep its activity and efficacy during an effective and safe hypoglycemia treatment in emergency conditions. Rapid Reconstitution Packages (RRPs) are handy technologies based on microfluidics platforms for rapid reconstitution of lyophilized biopharmaceutical drugs than can be used in time- critical therapies. RRPs were fabricated using computational simulation such as Computational Fluid Dynamics (CFD) that allows for an analytical methodology to maximize fluidic components for mixing, integrating both physical and chemical properties of targeted active ingredients and solvents. Devices were fabricated using 3D printing technology for micrometer structural precision and rapid prototyping. Glucagon was used due its instability and special features as the drug standard to evaluate the new RRPs generation. Current forms of glucagon cannot be kept for long periods of time due its unstable in aqueous solutions. Glucagon is a polypeptide hormone produced by alpha-cell of the pancreatic islet to increases blood glucose levels and relaxes smooth muscle of the gastrointestinal tract. This hormone was stored in lyophilized and aqueous form into the RRPs. Glucagon is essential in the treatment of severe hypoglycemia for which its rapid reconstitution is of supreme importance. RRPs efficiency and hormone stability were evaluated by HPLC to characterize glucagon release kinetics. Spectroscopy methods are also used. Hormone activity was monitored by Enzyme-Linked Immunosorbent Assays (ELISAs) exposing RRPs to various controlled temperature conditions. Experimental results showed that RRPs provide an effective reconstitution of glucagon and that its release kinetics is strongly correlated with computational modeling. The design and fabrication of RRPs can be adapted for others therapeutics applications by taking into account critical key point parameters (e.g., chemical and physical) to maximize efficiency, efficacy, reconstitution and controlled release kinetics of the active ingredients.
Gillian Hutcheon
Liverpool John Moores University, UK
Title: Polymeric nanoparticles for the pulmonary delivery of miRNA to treat Chronic Obstructive Pulmonary Disease (COPD)
Time : 14:10-14:30
Biography:
Dr Hutcheon completed her PhD in 1996 from University of Strathlcyde, UK and undertook postdoctoral studies At Nottinghsm University before her appointment as a senior lecturer at Liverpool John Moores University; in 2007 she was appointed as Reader in Biomaterials. She is chartered chemist and a Fellow of the Royal Society of Chemistry. She has published more than 35 papers in peer reviewed journals
Abstract:
Altered miRNA expression has been associated with both neoplastic and inflammatory lung diseases, including chronic obstructive pulmonary disease. RNA interference (RNAi) based interventions are promising for the therapeutic modulation of gene expression and small non-coding RNA molecules known as microRNAs (miRNAs) may be tractable targets for the treatment of lung disease. In this study, cationic polymeric nanoparticles (NPs) were prepared from poly (glycerol adipate-co-ω-pentadecalactone) via oil in water emulsion solvent evaporation method using DOTAP (%w/v). The particles were characterized for size, zeta potential (ZP) and A549 cell viability (MTT assay). The size and charge of the NPs was dependent on the concentration of DOTAP with an increase from 5% to 20% resulting in a decrease in particle size and polydispersity. Optiumum NPS of an equivalent size and polydispersity to those produced without DOTAP were prepared by the addition of 15% DOTAP increasing the ZP from -18.9±0.9 to +14.8±0.26 mV. Over 65% of A549 cells remained viable following 24 h exposure to the DOTAP NPs (1.25 mg/ml) and the NPs alone had little effect on cell viability. Fluorescently-labelled synthetic miRNA (40 μg/ml) was adsorbed onto optimum NPs which led to a slight decrease in ZP +11 mV, and approximately 77 % of miRNA was released in PBS after 24 h. Confocal microscopy using NPs with encapsulated nile red indicated uptake of the particles into the cells and further bioassays are currently ongoing. Overall, our results suggest that miRNA-coated NPs will be a useful formulation for future in vitro studies.
Shayan F Lahiji
Yonsei University, South Korea
Title: Microneedle delivery: a novel and minimally-invasive drug delivery system to overcome limitations of hypodermic needles
Time : 14:30-14:50
Biography:
Shayan F Lahiji has completed his BS and MS from Yonsei University (South Korea) and is currently doing his PhD at the same university. Because of his outstanding contribution to science and new novel delivery systems, he has been awarded in different fields of science for “The best poster presenter” from 3rd world biotechnology conference, “The best research award” from Yonsei University and “The best academic poster” from BK21 PLUS Research Symposium and more. He has published papers in reputed journals such as “Scientific Reports” from Nature Publishing Group and “Biomaterials” from Elsevier.
Abstract:
Transdermal drug delivery is regarded as an important route with high potential for drug delivery to overcome limitations of oral delivery and hypodermic injections. Among various delivery methods available, microneedles have gained interest due to their ability in delivering drugs with a high efficacy compared with topical application. Microneedles are referred to microscopic needles that are capable of delivering pharmaceutical compounds, proteins and even cosmetics into the skin in a minimally invasive manner. There are three main categories of microneedles; hollow, solid and dissolving. Dissolving microneedles are polymeric structures fabricated over a patch that encapsulate drug and deliver it into skin upon application. However, due to stiffness properties of skin, only small portion of microneedles get inserted into skin and the rest remains on the patch. Therefore, we developed a patch-less dissolving microneedle delivery system which delivers microneedles into skin through micro-pillar structures without causing pain in less than a second. We tested this sytem using insulin on diabetic mice and results showed that our micropillar based delivery system was capable of delivering insulin with approximately 60% higher efficacy than microneedles fabricated over patch and at a similar rate as hypodermic injection. Therefore, we believe that this system have a high potential to treat people suffering from diabetics in a minimally invasive manner without the need of hypodermic injection.
Chinnathambi Shanmugavel
National Institute for Materials Science, Japan
Title: Functionalized near-infrared quantum dots for biological applications
Time : 14:50-15:10
Biography:
Chinnathambi Shanmugavel has completed his PhD from Anna University. He was awarded the JSPS Post-doctoral fellowship to work under the guidance of Prof. Nobutaka Hanagata, National Institute for Materials Science, Japan. His research focuses on regulation of cellular functions using quantum dots for infectious diseases, allergy treatments, and cancer therapy.
Abstract:
As light emitting quantum dots (QDs) have been a noteworthy center of innovative work amid the previous decades. In the present study, water dispersion of the CdSe/ZnS quantum dots were accomplished by their encapsulation within polyethylene glycol (PEG)-grafted phospholipid micelles with biotin as a free end. The prepared near infra-read (NIR) QDs micelle permit photon infiltration through tissue and minimize the impacts of tissue autofluorescence. In addition, the micelle formation reduces the cell cytotoxicity and increses the fluorescence signal in the cell. For the separation purpose, we added iron oxide nanoparticle in the micelle core. This type of micelle easily uptake cancer cells without further modification, because it will enter the cancer tissue through blood vessel holes. The photostability of micelle under ultraviolet irradiation is stronger than free CdSe/ZnS quantum dots. The interaction of micelle with human serum albumin was studied using steady state and excited state fluroescence spectroscopy and the binding parameter was obtained with various temperature. Hydrophobic force and hydrogen bond stabilized the interaction between albumin and micelle. Furthermore, we checked cell viabilty and cellular uptake of prepared micelles using the following cell lines HeLa, RAW 267.4 and A549. There is no notable cytotoxicity observed micelle concentration up to 25 μg/mL. We observed fluorescence images of micelle using confocal laser scanning microscope. The observed fluorescence images clearly shows the high intensity of micelles after 24 h incubation. This methodology demonstrates the huge guarantee of quantum dots as a part of tests for multimodel imaging and therapy.
Rafael Bernad
Bicosome S.L., Spain
Title: Bicosomes: A smart skin drug delivery platform
Time : 15:10-15:30
Biography:
Rafael Bernad is a Biologist from the University of Oviedo in Spain. He has obtained his PhD in The Netherlands Cancer Institute studying the Nuclear Pore Complex and Nuclear Transport. His Postdoctoral Research focused in studying the Epigenetics of Centromeric Chromatin in the Spanish Cancer Research Institute. After 10 years involved in fundamental research, he moved to industry in 2010 where he played roles as Business Development and R&D. He has been involved in Drug Delivery development projects for injectable and topical pharmaceutical forms. He has recently joined Bicosome project.
Abstract:
Skin’s main function is to protect our body from external aggression. This is mainly achieved by a strong barrier function performed by the outer layer of the skin: The stratum corneum (SC). In contrast, most skin alterations and pathologies originate in the inner layers of the skin (Epidermis, Dermis or Hypodermis) and therefore require targeted treatments. Skin penetration is one of the biggest challenges for drug delivery. Most topical ingredients do not really penetrate the SC, acting on the skin’s surface and disappearing after a single wash. Other ingredients include chemical enhancers and/or other aggressive compounds that penetrate disrupting the skin barrier and causing damage. In both cases, efficacy and safety are compromised. Formulators of are facing the challenge to create skin care products able to penetrate gently the skin, remains there and deliver their content in the targeted layers. Bicosome platform offers a solution to these challenges. Structurally, Bicosomes are made up of internal smart biocompatible structures enclosed in a lipid vesicle protecting them and boosting their effects. Active molecules of many different natures can be incorporated to this platform. The smart structures of the bicosomes are small enough to penetrate the skin and self-aggregate into the tissue and grow being retained in specific layers. This induces a reinforcement of the skin structures and a targeted delivery. This delivery strategy allows a prolonged effect of actives because bicosome components retained in specific target layers remain there until this layer is lost following the natural desquamation process of the skin. These systems open a new and disruptive strategy, in which actives directed to the target layers and are remain retained exerting their action for days.
Hamid Mobedi
Iran Polymer and Petrochemical Institute, Iran
Title: In situ-forming drug delivery system for treatment of chronic osteomyelitis
Time : 11:55-12:15
Biography:
Hamid Mobedi has completed his PhD in Pharmaceutics at the age of 30 years from Mashhad University of Medical Sciences . He has published more than 40 papers in reputed journals and developed three NDDS products. He is the head of Novel Drug Delivery Systems (NDDS) Department in Iran polymer and petrochemical institute.
Abstract:
Bacterial bone infection, or osteomyelitis, poses a considerable problem for successful orthopedic involvement, that frequently leads to bone loss and the spread of infection to the surrounding tissues. Local delivery of high doses of antibiotics, minimizing potential systemic toxicity, is popular in treating osteomyelitis because it can facilitate the delivery of antibiotics by diffusion into avascular areas that are not accessible by systemic antibiotics therapy. The most widely applied material is polymethylmethacrylate (PMMA) beads loaded with antibiotic, which was proven to be successful in the treatment and prevention of osseous infections. An alternative approach is to use a biodegradable polymer, that is eliminating the need for a secondary surgical procedure to remove the foreign object. In addition, due to its degradation in the implantation area, the drug carrier does not prevent the formation of new bones. Nowadays, the controlled drug delivery systems that are based on polymeric solution have received considerable attention. In these systems, known as in situ-forming implants, drug release is controlled by the asymmetric membrane that are formed by polymer phase inversion. In this study effect of some factores like solvent water affinity and drug hydrophilicity on the release profile was investigated and prepared formulations were evaluated by drug release, morphology, injectibility and bactericidal assay. Finally, we prepared an in situ-forming implant with controlled amount of drug release in the first day and sustained release over 6 weeks. The concentration of antibiotic remained well above the minimum bactericidal concentration (MBC) in the theraputic period.
Biography:
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Abstract:
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Biography:
Sung Wan Kim is currently a Distinguished Professor of Pharmaceutics and Pharmaceutical Chemistry and a Distinguished Professor of Bioengineering. He was Director of the Center for Controlled Chemical Delivery at the University of Utah from 1985-2006. He received his B.S. and M.S. at Seoul National University, and his Ph.D. in Physical Chemistry at the University of Utah (under Professor Henry Eyring). Dr. Kim is a pioneer in drug delivery research and has engaged in his research since 1974 in the areas of hydrogels, biodegradable drug conjugates, self-regulating drug delivery and stimuli sensitive polymers. He also worked extensively in medical polymers, especially blood compatible polymers. Dr. Kim’s present research includes design of novel polymers for the delivery of protein drugs, cells and genes. Dr. Kim has received numerous awards; among them are the Terumo Award – Japan (2014), AAAS Fellow (2014), Research Achievement Award-Pharmaceutical Sciences World Congress (2004), Rosenblatt Prize (2003), Ho-Am Prize (2003), AACP Volwiler Award (2002), American Association of Pharmaceutical Scientists (AAPS) Dale Wurster Award (1998), the Controlled Release Society (CRS) Founders Award (1995), and the Clemson Basic Biomaterials Award (1987). These awards are the highest scientific awards from their respective societies. He is the Founder and served as Co-Chairman of the International Symposium on Recent Advances in Drug Delivery, Salt Lake City, UT, 1983-2005. In 2006, Dr. Kim received an honorary doctorate degree from the University of Twente. From 2004 to present, Dr. Kim is a Hanyang Distinguished Professor at Hanyang University. Dr. Kim has published over 650 papers and owns 35 U.S. Patents. He has trained over 130 scientists from 10 countries.Dr. Kim Has Been Elected To Two U.S. National Academies: The Institute Of Medicine in 1999 (As Of 2015 Changed To The National Academy Of Medicine) And The National Academy Of Engineering In 2003.
Abstract:
The disulfide-linked bioreducible polymer poly(cystaminebisacrylamide-diaminohexane) [CBA-DAH] was synthesized. Primary rat skeletal myoblasts were transfected with poly(CBA-DAH)/pCMV-VEGF165. MRI analysis of the treatment groups reveled a significant recovery of ejection fraction in the VEGF myoblast treatment over myoblasts only and ligation control. Apoptotic cell population reveled a significant attenuation of apoptosis in the myoblast only group but a higher attenuation in the VEGF myoblast group compared to ligation controls. This indicated that while myoblast implantation alone limits apoptosis in the myocardium, the VEGF myoblast group is producing a significantly higher protective effect. The work demonstrates that bioreducible polymers can successfully be used to transfect skeletal myoblasts with angiogenic factors. We proposed that the hMSCs delivered by our PLGA/PEI 1.8k (PPP) microparticles produce in vivo cardioprotective effects on post-infarct cardiac remodeling. We demonstrated that intramyocardial delivery of hMSCs by porous PPP particles in infarcted rats preserved engraftment of hMSCs in infarcted myocardium, cardiac geometry, and left ventricular systolic function. In addition, hMSCs-loaded PPP delivery augmented blood flow to coronary artery. The reduced infarct size of hMSC-loaded PPP delivery was followed by a decrease in fibrosis, protection from cardiomyocyte loss, and down-regulation of apoptotic activity. Furthermore, the increased angiogenesis and decreased myofibroblast density in the border zone of the infarct support the beneficial effects of hMSC-loaded PPP administration. These results of hMSC therapy delivered by PPP particles provide insight into the hMSC therapy translation in the treatment of acute myocardial infarct to human trials.
Caterina Guiot
University of Torino, Italy
Title: Physical fields may promote nanocarriers effectiveness in targeted drug delivery
Biography:
C Guiot is a Physicist with a PhD background in Physiology. Her research is in applied physics in medicine ranges from numerical modelling to ultrasound and nanomedicine. She published nearly one hundred papers in the above fields.
Abstract:
Nanotech resources have dramatically changed the drug delivery scenario. Due to the availability of nanocarriers which may be internalized by cells and release their cargo inside them, effectiveness is strongly enhanced and toxic side effects greatly reduced. The most critical aspect is the capability of reaching the target sites. Although the nanocarrier surface can be properly equipped with molecules with a very large affinity to the target cells, their systemic administration is ‘per se’ responsible of the fact that only a small nanocarrier percentage will reach the tissue of interest. This is a limitation for the drug bioavailability and release kinetics. Local or topical delivery methods would be therefore of great interest, but are scarcely feasible unless physical fields are used to enhance penetration and drug localization. Sonication with focused or unfocused ultrasound is a well known physical mean to improve the trespassing of membranes such as the skin, the Blood Brain Barrier (BBB), etc. Also static, low intensity magnetic fields may afford effective directionality in drug delivery. Particularly, oxygen and drug-filled nanobubbles for the delivery of levo-dopa and apomorphine in Parkinsonian patients can be addressed by ultrasonication of oral or nasal mucosae to reach as more proximally as possible the BBB. The ability of the nanobubble shells of chelating heavy metals in the cerebral liquids, which are overrepresented in Parkinsonian patients would be useful for both reducing their concentration and confer to the nanobubbles some magnetic properties which may help in directioning them outside from the BBB.
- Track 8: Physiological Considerations
Track 9: Vaccine Drug Delivery Systems
Track 10: Biotherapeutics-Drug Discovery and Development
Location: Melia Avenida America
Chair
Osama Ibrahim
Bio Innovation, USA
Co-Chair
Helen McCarthy
Queen’s University Belfast, UK
Session Introduction
Osama Ibrahim
Bio Innovation, USA
Title: Expression of shiga-like toxin fused to Vascular Endothelial Growth Factor (VEGF/SLT) in E. coli for targeting angiogenesis
Time : 11:50-12:10
Biography:
Osama O Ibrahim is a highly-experienced Principle Research Scientist with particular expertise in the fields of biochemistry, microbiology, molecular biology, and bioprocessing for both pharmaceutical and food ingredients. He was External Research Liaison for Kraft Foods with Universities for research projects related to bioprocessing and molecular biology. In the 2005, he accepted an early retirement offer from Kraft Foods and formed his own biotechnology company (Bio Innovation) providing technical and marketing consultation for new start-up biotechnology and food companies. He holds three bioprocessing patents and received his PhD in basic medical science (Microbiology, Immunology and Molecular biology) from New York Medical College. He is a Member of American Chemical Society, American Society of Microbiology, and Society of Industrial Microbiology since 1979.
Abstract:
Angiogenesis is a highly controlled process of growing new blood vessels under normal circumstances. However, in a large number of pathologies, such as solid tumor growth, angiogenesis is a crucial component of the disease process. Therefore, inhibitors of angiogenesis are being investigated as potential therapeutics for tumor growth. During angiogenesis endothelial cells of existing blood vessels undergo a complex process of reshaping, migration, growth, and organizing into new vessels. Vascular Endothelial Growth Factor (VEGF) is a central mediator of this process and acts via receptors whose expression is restricted almost exclusively to endothelial cells. Because of its selectivity, VEGF represents a unique vehicle for delivery of inhibitors of angiogenesis to endothelial cells. Among potential inhibitors of angiogenesis, the shiga-like toxin-1 (SLT-I) produced by E. coli O157:H7 has the advantage that endothelial cells appear to be particularly sensitive to its action. The hypothesis that combining an SLT-I toxin with VEGF as a delivery vehicle would serve as a highly selective and active inhibitor of angiogenesis. To this end, fusion proteins containing VEGF121 and two forms of shiga-like toxin-I (SLT-I) were developed and tested in vitro for activities that have the potential to inhibit angiogenesis in vivo. Plasmids encoding the fusion proteins VEGF121/A1 containing the catalytically active fragment of the SLT-I A subunit and VEGF121/A containing the full length A subunit of SLT-I were constructed in pET-29a and pET-32a systems. Escherichia coli BL21 (DE3) pLysS bacteria were transformed with the plasmid constructs for the expression of these two fusion proteins. Both purified fusion proteins inhibited the translation of luciferase mRNA as a reporter gene in vitro translation system, indicating that both fusion proteins retain the N-glycosidase activity of SLT-I. However, only VEGF121/A1 fusion proteins displayed the ability to induce auto-phosphorylation of the VEGF receptor KDR/FLK-1 and displayed a strong, selective growth inhibition of cultured cells expressing KDR/FLK-1 receptors. These results indicated that VEGF/SLT fusion proteins are promising therapeutic agents that can be developed into powerful and selective inhibitors of angiogenesis.
Helen McCarthy
Queen’s University Belfast, Northern Ireland
Title: A new technology for DNA vaccination: RALA peptide-mediated gene delivery via dissolving microneedles
Time : 12:10-12:30
Biography:
Dr Helen McCarthy obtained her PhD in 2000 from University of Ulster. She then took a Research Associate post in the field of prostate cancer gene therapy at the University of Ulster. In July 2004 she moved to the School of Pharmacy, Queen's University Belfast to take the post of Research Fellow on a cancer gene therapy project, within the newly established, Experimental Therapeutics research cluster. She obtained a lectureship within the School of Pharmacy in November 2006, then Senior Lecturer in 2011 and Reader in 2013. For the last 10 years Dr McCarthy’s research team have focused on the development of non-viral delivery systems for nanomedicine. These biomimetic systems are designed to overcome the extra and intracellular barriers, so that the macromolecular payload can be delivered at the destination site in order to exert the optimal therapeutic effect. Dr McCarthy has published widely (>50 research papers), holds several patents on delivery systems in the nanotechnology area and has given numerous invited conference presentations. She has obtained significant research grant income from MRC, BBSRC, EPSRC, Cancer Research UK, Prostate Cancer UK, Breast Cancer Campaign, Royal Pharmaceutical Society of Great Britain, The Royal Society, National Science Foundation, Invest NI and Touchlight Genetics. She has also collaborated extensively both nationally and internationally and sits on the editorial board for Cancer Nanotechnology.
Abstract:
Cervical cancer has the second highest mortality rate amongst women worldwide, despite the production of recombinant protein HPV vaccines. Limited access in poorer regions, the prophylactic nature of current vaccines and poor patient compliance contribute to a rising incidence. Furthermore, the current vaccine is not effective for those patients with pre-existing HPV lesions. DNA vaccination evokes both therapeutic and prophylactic responses. The bottleneck in the DNA vaccination market lies in an effective delivery technology. The ‘solution’ to this problem is in the two-pronged approach of our technology: (i) a peptide delivery system, termed RALA, that is able to wrap the DNA into nanoparticles, protect the DNA from degradation, enter cells, disrupt endosomes and deliver the DNA to the nucleus and (ii) a microneedle patch (MN) that will house the nanoparticles within the polymer matrix, painlessly breach the skin’s stratum corneum barrier and dissolve upon contact with skin interstitial fluid thus releasing the nanoparticles into the skin to the antigen presenting cells. Using our novel technology platform we have created a DNA vaccine for cervical cancer in a dissolvable microneedle patch. More specifically the MN patch is loaded with RALA/E6-E7 nanoparticles and this study demonstrates stability, functionality and a prophylactic and therapeutic response to cervical cancer tumours in vivo. The RALA/E6/E7 nanoparticles were characterized in terms of gel retardation, size and zeta-potential analysis and transmission electron microscopic imaging. The functionality of the RALA/E6-E7 nanoparticles within the polymeric microneedle matrix was assessed by analysis of transfection efficacy in fibroblast NCTC cells via western blot analysis. Cellular toxicity was also assessed via WST-1 assay. C57/BL6 mice were immunized with the RALA-E6/E7 in a prime-boost-boost regimen and blood serum was isolated to measure specific IgG responses and IFN-γ levels via ELISAs. C57/BL6 mice were also immunised with the MN-RALA/E6-E7 patches and challenged with cervical cancer. A therapeutic response study was performed in vivo. Finally the RALA/E6-E7 nanoparticles were lyophilised to increase the dose that can be loaded into the MN patch. Results proved that RALA was essential for stability of the E6-E7 DNA in PVP and that MN-RALA/E6-E7 evokes a more consistent humoral mediated immune response. Tumour challenge studies indicate the MN-RALA/E6-E7 vaccine patch is preventing the uptake of tumours and treating established tumours. Doses greater than 50 μg were achieved from a single MN patch. We have, therefore, created a fully functional prototype MN/RALA/E6-E7 DNA vaccine for cervical cancer.
José Crecente Campo
Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Spain
Title: Nanotechnology and mucosal vaccines
Time : 12:30-12:50
Biography:
Dr. José Crecente is a researcher at the University of Santiago de Compostela (USC). He holds several degrees in Industrial Engineering, Science Food and Chemistry apart from a master degree in Drug Discovery and Development and a PhD in Organic Chemistry. He has also worked as a visiting scientist at Cambridge University in the group of Prof. Steven Ley. Over the last 3 years Dr. Crecente has been associated to the laboratory of Prof. Alonso, at the USC, where he has been involved in the formulation of proteins and antigens. Currently, he is involved in 4 vaccine-related projects, among them a NIH project and a EU (NANOPILOT) project, both oriented to the preclinical development and scaling-up of nanovaccines.
Abstract:
Vaccination has been, without any doubt, the greatest success of medicine in preventing diseases. Infections that centuries or even decades ago caused decimation of whole cities and countries nowadays are old ghosts of the past or have much less impact in human beings. In the constant effort of science to increase quality of life, vaccines based on living or attenuated microorganisms that provoked severe side effects have evolved to vaccines based on safer antigens, like purified proteins, peptides and plasmids. However, these last compounds are much less immunogenic and for that reason the use of adjuvants is becoming imperative in the development of modern vaccines. Among these adjuvants, nanoparticulated systems have emerged as ideal candidates thanks to the advantages they can offer like (i) to protect the integrity of the antigen, (ii) to improve and prolong the antigen presentation to the immune system cells and (iii) to modulate the immune response towards the cellular or humoral arm. Besides, nanosystems can be an ideal platform to administer vaccines through the mucosal routes with some important benefits like (i) better mucosal response, (ii) needle-free vaccination, (iii) better compliance of the patient, and (iv) easier production. Nanotechnology is providing us more and more sophisticated platforms like nanoparticles, ISCOMs, nanocapsules, bilosomes, etc. and probably, in the near future we will see a mucosal nanovaccine in the market.
John Higgins
Merck Research Labs, USA
Title: Drug delivery and solid state chemistry at the drug discovery-development
Time : 14:40-15:00
Biography:
John received a BS in biochemistry from Albright College and his Ph.D. in synthetic organic chemistry from Brown University. After completing a Postdoctoral Fellowship at the Sloan-Kettering Cancer Institute in NYC in the departments of Positron Emission Tomography and Neurology, he joined the Medicinal Chemistry Discovery group at Johnson Matthey Biomedical. There he worked on Pt-based antitumor drugs and diagnostic radio-imaging agents. He later moved on to drug development, in positions of increasing responsibility at J&J and Sanofi Aventis. For the past 15 years he and his teams have specialized in the areas of drug delivery and solid state chemistry, focused at the interface of drug discovery and development. His specific expertise in drug delivery lies in the area of enhancing the solubility of insoluble compounds, where he has successfully introduced a wide range of methods into drug discovery space. More recently, he has been active in the design of prodrugs for improving physicochemical properties or targeting for specific disease states. He currently is a Senior Principal Scientist and Global Technology Lead in the Discovery Pharmaceutical Sciences department at Merck Research Labs. Spanning his 25 year career, he is co-inventor on 13 US Patents and author of numerous publications and book chapters in the fields of organic, solid state & medicinal chemistry and drug delivery.
Abstract:
ver the past decade, scientific and business needs have pushed Pharma to more closely align drug discovery and drug development efforts in order to bring optimal preclinical drug candidates (PCCs) forward. Towards this end, Pharma development chemists at Merck now routinely provide innovative rationally designed drug formulations ranging from nanoparticles to amorphous dispersions for key preclinical animal studies. They also work closely with medicinal chemists to optimize PCCs’ physicochemical properties and identify a crystalline phase that has appropriate characteristics that will allow for good performance in pre-clinical safety studies and clinical formulations. In all cases, miniaturization and state-of-the art characterization methods are essential. Early investment in these areas can significantly shorten the time to the clinic and help avoid ugly surprises related to API phase and exposure. One of the most exciting aspects of working in this space is the many opportunities for innovative collaboration between biologists, chemists, pharmacologists, etc., investigating new drug delivery modalities and administration routes in a wide range of preclinical species. This presentation describes the unique tools a Merck uses in discovery space and shows some examples where partner groups from Discovery and Development worked together to increase the speed of drug lead identification, biopharmaceutical optimization and the PCC clinical approval process.
Fatmah Alasmary
King Saud University, Saudi Arabia
Title: Synthesis and evaluation of selected benzimidazole derivatives as potential antimicrobial agents
Time : 12:50-13:10
Biography:
I completed the PhD from University of Bradford and I am a chemist who has taught Chemistry in the Department of Chemistry, College of Science, King Saud University for more than 5 years. I interested in research and follow recent discoveries in science, particularly Chemistry, by reading the literature.
Abstract:
A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. In particular, some compounds displayed antibacterial activity against two methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentrations (MICs) comparable to the widely-used drug ciprofloxacin. The compounds have some common features; three possess 5-halo substituents; two are derivatives of (S)-2-ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl)-1H-benzo[d]imidazole and (1H-benzo[d]imidazol-2-yl)methanethiol. The results from the antifungal screening were also very interesting: 23 compounds exhibited potent fungicidal activity against the selected fungal strains. They displayed equivalent or greater potency in their MIC values than amphotericin B. The 5-halobenzimidazole derivatives could be considered promising broad-spectrum antimicrobial candidates that deserve further study for potential therapeutic applications.
Afaf Benhouda
University of Batna, Algeria
Title: Evaluation of hepatoprotective and anti-peritonitis activities of methanolic extract of Umbilicus rupestris L. in vivo.
Time : 15:20-15:40
Biography:
Afaf BENHOUDA has completed his PhD at the age of 27 years from Algeria University and she did her PHD at University of Degli Salerno –Italy and the dempartment of Farmacia Fedderico II Italy. She published 4 articles ans she has 15 internationan and national congres in Cybrus, Antalya, Edirna, Istanbul, Marrakech, Pekin.
Abstract:
The present study is to evaluate the protective effect of methanolic extract of the leaves of the plant Umbilicus rupestris against hepatotoxicity induced by the ethanol and also to evaluate th inflammation induced by the carrageenan. In heptoprotective activity, five groups of 4 rats were treated respectively with distilled water, absolute ethanol ,URMeOH (100 mg / Kg b.w.), URMeOH (200 mg / Kg b.w.) and quercetin used as the reference standard, these treatments were administered orally 30 minutes before the administration of absolute ethanol for 14 days. The results showed that administration of EtOH increased significativeley the level of biochemical parameters TGO, TGP, ALP and BTof pathologic control but the effect of the extract shows that the oral adminstration of (100 and 200 mg / Kg) and quercetin caused a significant decrease (p≤0.05) of these parameters. For anti-inflammatory activity, Wistar rats were divided into four groups of four rats. The extract was administered orally with doses (100 and 200 mg/ kg b.w) and indomethacin (50 mg / kg) then the Carrageenan (2%) was injected intraperitoneally1 hour later.The protective effect of the extract was evaluated by measuring the number of leukocytes recruited into the peritoneal cavity.The pretreatment with the extract(100 and 200mg /kg b.w.) decreased significantly the number of leukocytes (P≤0.05) compared to the control group.
Biography:
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Abstract:
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Biography:
Abstract:
The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was studied. By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar. At neutral pH, binding of TT conjugates to AlPO4 was facilitated through the carrier protein, with only weak binding of AlPO4 to CRM197 being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM197–conjugates. This was verified in AlPO4 formulations containing DTwPeHib, where the adsorption of TT-conjugated Hib was higher than CRM197–conjugated Hib. At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions. Phosphate ions reduced the binding of the conjugates to the adjuvants. These patterns of adjuvant adsorption can form the basis for future formulation studies with individual and combination vaccines containing saccharide-protein conjugates.
Muhammad Akhtar
The Islamia University of Bahawalpur, Pakistan
Title: In vivo kinetics of modified release gastroprotective combination in healthy male volunteers
Biography:
Muhammad Akhtar has completed his PhD in the year 2014 from The Islamia University of Bahawalpur, Pakistan. He is currently working as an Assistant Professor of Pharmaceutics at Department of Pharmacy, The Islamia University of Bahawalpur. He has published more than 20 research and review articles in reputed national and international journals and has been serving as reviewer for research journals of good repute. He has university teaching experience of more than 10 years to teach the students of PharmD and MPhil (Pharmacy). He has presented his research at national and international conferences.
Abstract:
The study was aimed to evaluate pharmacokinetic parameters of sustained release combined formulation of ibuprofen and misoprostol tableted microspheres. The study was conducted in 18 healthy male volunteers. A single dose as tablet was administered through oral route. The plasma concentrations of drugs were assessed by development of reverse phase HPLC method and blood samples were taken over a period of 12 h post drug administration. Non-compartmental method of analysis was used for evaluation of pharmacokinetic parameters. Maximum plasma drug concentration (Cmax) and time (tmax) to reach Cmax were determined directly from the data. Area under plasma concentration time curve from time zero to time of last quantifiable concentration (AUC0-t) was calculated using linear trapezoidal rule. In addition, absorption parameters were also calculated. Kinetica® software version 4.4.1 was used for these calculations. Computer based MS-Excel was used to determine mean ± SD values. The current HPLC method was found suitable for simultaneous determination of ibuprofen and misoprostol. The Cmax values (mean ± SD) of 26.68±2.32 and 0.17±0.01 for ibuprofen and misoprostol were observed, respectively. The values (mean ± SD) of T¬max and AUC0-∞ were 1.89±0.47 and 179.81±22.87 for ibuprofen while 1.36±0.54 and 0.84±0.04 for misoprostol, respectively. The current study reported improved bioavailability and estimation of the quantifiable concentrations of both drugs in plasma for a prolonged period of time by successfully developing a fixed-dose combination of both IBN and MIS as tableted microspheres.
Tejeswararao Dharmana
GMR Institute of Technology, India
Title: Synthesis and in vitro anti-candida activity studies of novel quinoxaline derivatives
Biography:
Tejeswararao D has completed his PhD from Indian Institute of Chemical Technology, Hyderabad. He is working as Assistant Professor in GMRIT, Rajam. He has published 2 papers in reputed journals and presented in 8 proceedings. He is the Chairman of REES Society (non-profit organisation).
Abstract:
A diversity-oriented synthesis has been developed for facile construction of a library of quinoxaline derivatives. The synthetic protocol is suitable for generating quinoxaline derivatives with various structural motifs for exploring the desired activity. From this initial library, we have observed few derivatives showed significant activity against different strains.
- Young Researchers Forum Day 2
Location: Melia Avenida America
Chair
Drazen Raucher
University of Mississippi Medical Center, USA
Co-Chair
Kang Choon Lee
SungKyunKwan University, Republic of South Korea
Session Introduction
Ana Rute Neves
University of Porto, Portugal
Title: Challenges and advances in oral drug delivery using lipid-based nanoparticles
Biography:
Ana Rute Neves (PhD Pharmaceutical Sciences) is a Post-doctoral researcher at Research Unit UCIBIO/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Portugal. She got her MSc in Biochemistry at the University of Porto in 2009. After 1 year of working in Angelini Pharmaceuticals Company she got her PhD in Pharmaceutical Sciences at Faculty of Pharmacy of the University of Porto in 2015. Currently her research focuses on the development of nanopharmaceuticals (lipid nanoparticles) as drug delivery systems to create new and more efficient therapies for a range of diseases and administration routes.
Abstract:
Oral administration is the preferred route for drug delivery and nanotechnology represents a novel strategy for protection and transport of hardly soluble, chemically unstable and poorly permeable drugs through the gastrointestinal tract, in order to improve their oral bioavailability. Here, lipid-based nanoparticles have been studied as promising tools for the transport across the intestinal barrier. All nanosystems present similar size (~180 nm) and surface charge (<30 mV). A stability study was conducted simulating the gastrointestinal tract fluids. The cellular uptake, internalization pathways and transcytosis routes were investigated using Caco-2 cells as a model of the intestinal barrier since after growth these cells form confluent and differentiated monolayers with microvilli, tight junctions and transport systems. Nanostructured lipid carriers show a higher cellular uptake and permeability across the barrier, while solid lipid nanoparticles may enter cells faster than the former. The internalization of lipid nanoparticles occurs mainly through a clathrin-mediated endocytosis mechanism, although caveolae-mediated endocytosis is also involved in the uptake. Both lipid nanoparticles are able to cross the intestinal barrier by a preferential transcellular route.
Vanessa Gonçalves
iBET, Portugal
Title: Novel Alginate-Chitosan aerogel fibers for potential wound healing applications
Time : 15:45-16:00
Biography:
Vanessa Gonçalves has completed her integrated master degree in Pharmaceutical Sciences in 2010 at University of Lisbon. She is currently a PhD co-tutela student at ITQB-UNL/iBET and University of Valladolid with the thesis “Overcoming CNS-barriers by the development of hybrid nanostructured systems for nose-to-brain drug delivery using precipitation clean technologies”. Her current interests are - Supercritical Fluids/High Pressure Processes, - the development of multilayered and hybrid particles, with strong mucoadhesive properties as drug delivery systems for nose-to-brain administration and - aerogels as drug delivery systems.
Abstract:
Wound healing it’s a complex and dynamic biological process. In recent years, the development of new wound dressing products from marine sources is gaining increased interest due to their unique properties such as antimicrobial activity (e.g. chitosan) or the capacity to provide a moist environment (e.g. alginate). Moreover, aerogels are porous structures with large surface area in which it is possible to achieve high drug loadings. In this work, newly alginate-chitosan aerogel fibers for wound healing application were prepared by emulsion-gelation method and further dried with supercritical CO2. The morphology and specific surface area of the final fibers were studied by scanning electron microscopy and Brunauer–Emmett–Teller method, respectively. Furthermore, menthol, a monoterpene with antimicrobial activity, was loaded into the fibers by supercritical adsorption and quantified by gas chromatography analysis. Finally, the antimicrobial activity of alginate-chitosan fibers and alginate-chitosan fibers loaded with menthol were evaluated and its possible cytotoxicity was studied using human fibroblasts.
Benedetta Santini
University of Milano-Bicocca, Italy
Title: Cream formulation impact on topical administration of engineered colloidal nanoparticles
Time : 16:00-16:15
Biography:
Benedetta Santini is graduated in Pharmacy in 2013, and now she is following the second year of the PhD in Material Science and Nanotechnology at University of Milano-Bicocca. She spent six months at the King’s College of London as visiting student in Maya Thanou’s research group. Till now, she has published five papers
Abstract:
While the nanoparticles intravenous administration is the most prevalent practice for drug delivery, the transdermal penetration is still poorly understood and this important administration method remains almost unexplored. In the present study, we aim to explore the topical administration in order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions. We have synthesized iron oxide nanoparticles (MNP) coated with an amphiphilic polymer and included a water-in-oil emulsion formulation. We compared the skin penetration routes of the nanoemulsion with the colloidal nanoparticles suspension. Transmission and scanning electron microscopies pointed out that the amphiphilic nanoparticles (PMNP) cream formulation allowed a more efficient penetration through all the skin layers compared to suspension formulation, involving both the intracellular and intercellular pathways, in addition to the follicular one. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry (ICP-MS). In vivo experiments showed that the subcutaneous NPs administration resulted in preferential phagocytic uptake and migration to draining lymph nodes, while cream formulation favoured the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics. The obtained data suggested that combining PMNP amphiphilic character with cream formulation improved the intradermal penetration of nanoparticles
Sahar Awwad
UCL School of Pharmacy, UK
Title: The PK-Eye: A novel in vitro aqueous flow model to evaluate ocular pharmacokinetics
Time : 16:30-16:45
Biography:
Sahar Awwad completed both her Bachelors in Pharmacy and MSc in Drug Delivery. She is in the final year of her PhD at UCL School of Pharmacy and UCL Institute of Ophthalmology, under the supervision of Professor Steve Brocchini and Professor Sir Peng Tee Khaw.
Abstract:
Much effort globally is focused on developing the next generation of therapeutic antibodies and other long acting therapeutics to treat ophthalmic diseases. Most treatments must be administered by intravitreal injection, so an important goal is to develop medicines with an extended residence time within the eye. The development of prolonged acting protein-based therapies is limited by the formation of anti-drug antibodies (ADAs) in animal models. We have developed and validated a two-compartment, aqueous outflow model called the PK-Eye to be used for ocular drug development. The model has been designed to aid pre-clinical development by providing an estimate of human ocular pharmacokinetics of protein therapeutics. The model is also appropriate for evaluating long-acting dosage forms, such as suspensions, inserts and devices. This talk will describe new strategies for extending the half-life of drugs for ophthalmic use and their rapid evaluation in the PK-Eye.
Olga Gawrys
Mossakowski Medical Research Centre PAS, Poland
Title: Cationic derivatives of polyisoprenoid alcohols for liposomal drug delivery
Time : 16:45-17:00
Biography:
Olga Gawrys is a young scientist from Poland. Her academic interests relate to renal function, experimental medicine and liposomal drug carriers. She is a graduate of the Institute of Biotechnology (Warsaw University of Technology) with M.Sc. in Chemical Biotechnology – Drugs and Cosmetics. In 2015 she completed her PhD in Medical Sciences, in the discipline of Medical Biology (MMRC PAS). Recently she published three papers and presented her work at a variety of conferences. Twice she received a scholarship for the best PhD students of the MMRC PAS and a scholarship for PhD students carrying out applied research projects (EU).
Abstract:
Polyisoprenoids represent a large and diverse class of naturally occurring hydrophobic polymers, found in almost all living organisms. These linear compounds, constructed of 5 to more than 150 isoprene units, are commonly divided into dolichols (with hydrogenated α-bond) and α-unsaturated polyprenols. Polyisoprenoid alcohols play numerous roles in cells but above all, as structural components of cellular membranes, they modulate their properties. Biophysical studies proved that polyisoprenoids act as membrane modulators by influencing their fluidity and permeability. Latest research demonstrated that semi-synthetic, cationic derivatives of polyisoprenoid alcohols (called amino-prenols, APrens) possess lipofecting properties, because they facilitate the transfer of genetic material towards the cells. Amino-prenols were obtained by chemical modification in that hydroxyl group on α end was replaced by a quaternary ammonium group. This generated specific properties whereby these cationic lipids can influence biological membranes more easily and effectively. Hence the idea to use amino-prenols as components of liposomal carriers of drugs and genetic material. In the first stage of our study we tested potential toxicity of novel carriers with particular emphasis on their impact on renal function. In the next steps we examined usefulness of newly designed carriers for liposomal delivery of various drugs. Obtained results lead us to suspect that amino-prenols can be used as components of drug carriers, not only augmenting the biodistribution of active substances, but also improving the stability and loading capacity of liposomes. In the future we plan to further study amino-prenols in an attempt to enhance gene expression in vivo.
Merari Chevalier
CoMP-INTEMA- Universidad Nacional de Mar del Plata, Argentina
Title: Polymeric particulated carriers in drug delivery: Obtention, study and characterization
Time : 17:00-17:15
Biography:
Merari Tumin Chevalier has completed a 5 years degree in Chemistry from National University of Mar del Plata. Currently, she is working on her PhD thesis at the Research Institute in Materials Science and Technology (INTEMA)- CONICET (Argentina), particularly in the Group of Polymer Matrix Composite Materials led by Dra. Vera Alvarez. The goal of her work is to develop and study effective biopolymeric drug carriers. At the present time, she is doing a six month residence in the Polymer Science and Technology Institute (ICTP)-CSIC (Madrid) in order to acquire new knowledge regarding the preparation and characterization of polymeric nanoparticles
Abstract:
Over the past decade, significant progress has been made in the development of new pharmaceutical technology platforms based on different kind of systems. Therapeutically effective and patient-compliant drug delivery systems continuously lead researchers to design novel tools and strategies. In particular, polymeric micro and nanoparticles are micron and submicron size entities which can be made from a wide variety of natural and synthetic polymers. Due to particle’s ability to improve the efficiency of current therapeutic treatments, this type of devices are being extensively studied and used as drug carriers and controlled release systems in the field of biomaterials, medicine and pharmacy. Different polymeric particulate drug delivery systems have been obtained and studied. Paricularly, considering biopolymers capability for high loading drugs and to modulate drug release, this work attempts to study the physicochemical and biopharmaceutical properties of PLA/PEG-b-PLA, PLGA and PLLA particulated systems that could carry active ingredients of interest. The obtained systems were fully characterized by scanning electron microscopy (SEM), thermo gravimetric analysis (TGA), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Encapsulation efficiency and in vitro release profiles of each system was also determined by HPLC technique showing that there are potential applications of these polymeric carriers to solve problems and improve existing therapies in the field of health
Meliha Ekinci
Ege University, Turkey
Title: Cell incorporation studies with 99mTc labeled methotrexate loaded chitosan nanoparticles for breast cancer diagnosis
Time : 17:15-17:30
Biography:
Meliha Ekinci received her master degree in Radiopharmacy from Ege University (Turkey) in 2015. She is currently a Research Assistant at Radiopharmacy Department and also a doctoral student at Biopharmaceutics and Pharmacocinetics Department, Ege University. She has already published 4 papers in reputed journals. Her research interest is to radiolabeled and evaluated newly developed radiopharmaceuticals for diagnosis of different cancer types.
Abstract:
The aim of this study is to evaluate newly developed radiopharmaceutical’s (99mTc-MTX-CSNPs) incorporation to human breast cancer (MCF-7) and human keratinocyte (HaCaT) cell lines for breast cancer diagnosis. For this purpose, methotrexate (MTX) loaded chitosan nanoparticles (CSNPs) were prepared by ionic gelation process, storaged during 6 months and evaluated in terms of particle size, polydispersity index value and zeta potential. Produced MTX-CSNPs were radiolabeled by 99mTc with high labeling efficiency (>90%). Then, newly developed radiopharmaceutical’s Target/Non Target ratio was investigated with cell culture studies by using MCF-7 and HaCaT cell lines. Results demonstrated that the incorporation of 99mTc-MTX-CSNPs in breast cancer cells was found about 2-times higher than normal cells. So, 99mTc-MTX-CSNPs might be used for human breast cancer diagnosis in nuclear medicine patients. (The authors thank to Ege University, Scientific Research Projects Comission (Project number: 14/ECZ/037) and Aliye Uster Foundation for financial supports.)
Jesus Izaguirre Carbonell
Tokyo University of Science, Japan
Title: Novel anticancer agent, SQAP, binds to focal adhesion kinase and modulates its activity
Time : 17:30-17:45
Biography:
Jesus Izaguirre Carbonell obtained his degree in pharmacy at Universidad Miguel Hernandez in Spain. Thereafter, he moved to Japan where he is currently completing his PhD at Tokyo University of Science under Prof. Sugawara supervision and where he also obtained his master degree. He has published 4 papers for obtaining his PhD degree including renowed journals.
Abstract:
SQAP is a novel and promising anticancer agent that was obtained by structural modifications from a natural compound. Previous assays demostrated that SQAP inhibits angiogenesis in vivo resulting in increased hypoxia and reduced tumor volume with low side effects. In this study, the mechanism by which SQAP modifies the tumor microenvironment was revealed through the application of a T7 phage display screening. This approach identified five SQAP-binding proteins including sterol carrier protein 2, multifunctional enzyme type 2, proteasomal ubiquitin receptor, UV excision repair protein and focal adhesion kinase (FAK). All the interactions were confirmed by surface plasmon resonance analysis. Since FAK plays an important role in cell turnover and angiogenesis, the influence of SQAP on FAK was the principal goal of this study. We analyzed FAK-SQAP binding through a docking assay. Moreover, SQAP decreased FAK and FAK’s downstream signaling phosphorylation in addition to cell migration in human umbilical vein endothelial cells and A549 cancer cells. These findings suggest that inhibition of FAK phosphorylation works as the mechanism for the anti-angiogenesis activity of SQAP.
- Young Researchers Forum Day 3
Location: Melia Avenida America
Chair
Osama Ibrahim
Bio Innovation, USA
Co-Chair
Helen McCarthy
Queen’s University Belfast, UK
Session Introduction
Stephen Loughran
Queens University Belfast, Northern Ireland
Title: Development of a peptide-based, multifunctional gene delivey vector for metastatic prostate cancer
Time : 13:55-14:10
Biography:
Stephen Loughran was awarded a First Class Masters in Pharmacy Hons by Queen’s University Belfast in 2011. He is currently in his final year of a PhD research project which focuses on the design of multifunctional peptide vectors capable of delivering plasmid microRNA to metastatic prostate cancer. Stephen has two publications to date.
Abstract:
RALA is a 30mer, arginine-rich, amphipathic peptides with both cell-penetrating and endosomolytic properties. When mixed with plasmid DNA it condenses to form small, serum-stable nanoparticles which, when administered in vivo, are capable of transfecting cells. However, bioavailability in vivo was limited to the lungs and liver of treated mice. In order to improve nanoparticle pharmacokinetics, polyethylene glycol (PEG) 5K was conjugated to the C-terminus of the RALA peptide and the resulting conjugate (RALA-P) was characterized in vitro. Disappointingly, activity in vitro was nullified following addition of PEG which lead us to adopt an alternative strategy that involved mixing of RALA-P with native RALA at various w/w ratios in an attempt to restore cellular level activity without compromising pharmacokinetic benefits instilled through the addition of PEG. The resulting nanoparticle exhibited improved salt stability at physiological concentrations of NaCL and was also capable of transfecting cells in vitro. To test biodistribution of the modified nanoparticle, various w/w ratios of RALA/RALA-P containing plasmid fire-fly luciferase were administered to tumour-bearing mice in order to determine whether introduction of PEG in this way could enable transfection in vivo, augment accumulation in the tumour by EPR and reduce accumulation in off-target organs. The results demonstrate a significant reduction in accumulation in the liver and lungs of treated mice and an increase in tumour expression for RALA/RALA-P nanoparticles as compared to RALA only.
Hinojal Zazo Gamez
Universidad of Salamanca, Spain
Title: Gold nanoparticle for macrophage targeting of stavudine
Time : 14:10-14:25
Biography:
Zazo H is Licensed in Pharmacy and Post-Graduate in design, manufacture and testing of pharmaceuticals by the University of Salamanca, Spain. Nowadays, she is doing the PhD in pharmaceutical technology, in the same univeristy funding by the Spanish goverment, and she has done a research stay in the Department of Medicine III, RWTH Aachen. She is currently working as Assistant in the Department of Pharmacy and Pharmaceutical Technology, University of Salamanca.
Abstract:
Globally, there are millions of people living with HIV. Although the curret treatment allows controlling the infection, drugs do not efficiently reach target cells such as macrophages which serve as a depot for HIV. It has been proposed drug delivery systems such as nanoparticles to increase drug intracellular penetration. By this way, stavudine gold nanoparticles have been developed and their upke by human primary macrophages has been studied. The coupling of stavudine to the nanoparticles was checked by UV-Vis spectroscopy and zeta potential. Human primary monocyte-derived macrophages were incubated for 24 hours with different concentrations of stavudine gold nanoparticles. Nanoparticle concentrations evaluated for the cellular viability ranged from 0.025 to 25 µg Au/mL with only the highest concentration being slightly cytotoxic for the cells. Their uptake by the cells was studied using Transmission Electron Microscopy (TEM), the intracellular concentration of nanoparticles using Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) and the stavudine uptake was quantified indirectly by Ultra-Presure Chromatography UV spectrosopy (UPLC). The absence of a peak at 530 nm, characteristic of naked gold nanoparticles, in the stavudine-gold nanoparticles spectrum together with the significant change in the ζ-Potential displayed the presence of stavudine coupled to nanoparticles. ICP-MS-based intracellular quantifications of nanocarriers revealed the influence of the nanoparticles concentration in the kinetic of the uptake. UPLC-UV results show that the stavudine uptake after 24 h is deeply higher using gold nanoparticles as carriers. Therefore, stavudine gold nanoparticles, represents a novel nanotechnological strategy to target macrophages, which are of potential interest for HIV therapy.
Shrawan Baghel
Waterford Institute of Technology, Ireland
Title: An investigation into the stability and aqueous solubility of amorphous solid dispersions of BCS class II drugs
Time : 14:25-14:40
Biography:
Shrawan Baghel is currently doing PhD in “Novel technologies and optimized formulations for delivery of solid dispersion of BCS class II drugs”at Pharmaceutical and Molecular Biotechnology Research Center (PMBRC), Waterford Institute of Technology. He is the winner of Science Foundation Ireland scholarship for this project in collaboration with Synthesis and Solid State Pharmaceutical Centre. The main aim of this project is to gain an insight into the mechanistic and molecular aspects of solid disperison prepared by spray drying, hot melt extrusion and supercritical fluid process using DSC, XRD and NMR.
Abstract:
Amorphous solid dispersions have shown the potential to offer higher apparent solubility and bioavailability of BCS class II drugs. Drug stability, drug-polymer miscibility and drug supersaturation are the fundamental requirements for the successful design and development of such systems. The main objectives of this work are to study amorphous drug crystallization kinetics, assess a theoretical approach for the estimation of drug stability, drug-polymer interaction and miscibility on the basis of Flory-Huggins (F-H) theory and the role of polymer in maintaining drug supersaturation in dissolution media. Firstly, the relevance of fragility and glass forming ability to recrystallization of amorphous drugs is assessed. Secondly, the non-isothermal crystallization kinetics of model systems was also analysed by statistically fitting the crystallization data to 15 different kinetic models and the relevance of model-free kinetic approach has been established. Thirdly, a comprehensive investigation of binary and ternary F-H theory of amorphous solid dispersions of model drugs and polymers was conducted using modulated differential scanning calorimeter, dynamic vapour sorption and X-ray diffraction. The simplified relationship between F-H interaction parameter and temperature was established. This enables us to generate free energy of mixing curves at different temperature and finally the spinodal curve. Furthermore, a three-component F-H model was employed to analyse the moisture sorption behaviour of solid dispersions. It is also used to estimate the F-H interaction parameter of drug and polymer in the presence of moisture since it does not require a priori knowledge about binary interaction parameters between drug and polymer. Finally, the role of polymers in generating and maintaining drug supersaturation in dissolution media has also been investigated. Thus, this research work involves a multidisciplinary approach to establish crystallization tendency/kinetics and F-H theory as stability predictors for amorphous drug formulations.
Muhammad Irfan Alam
University of Sunderland, UK
Title: Local mucoadhesive drug delivery approach for furazolidone against Helicobacter pylori
Time : 14:40-14:55
Biography:
Muhammad Irfan Alam is a PhD student at the University of Sunderland, UK. Research project is about “Mucoadhesive and mucopenetrative micro- and nano-particulate drug delivery systems of antibiotics to target Helicobacter Pylori in stomach”. I have completed M.Phil, microbiology, in 2009 and worked as a lecturer in Pak International Medical College for two years.
Abstract:
Helicobacter pylori in stomach is considered as one of the major challenges for the clinicians in terms of resistance. Due to emergence of resistant strains 60-70% of eradication rate is decreased with conventional triple therapeutic regimen. Short resident time of anti Helicobacter pylori drug also leads to failure in complete eradication of the microbe. In the current study, the use of furazolidone mucoadhesive formulations (for local drug delivery approach) to increase the residence time of this antibiotic was studied to overcome above mentioned shortcomings. Two different approaches of mucoadhesive formulation were optimized in terms of residence time and pH of the surrounding environment to attain the desired drug concentration for effective length of time. One of the approach used comprise of polymer coated microparticles and the other consists of mucoadhesive liposomes. Chitosan was used as a mucoadhesive polymer in both approaches and the formulations were investigated on two different pHs. For liposomal mucoadhesion affectivness, fluorometry assay was performed by using coumarin-6 as Fluorophore and the results were further confirmed by the florescence microscopy. Colorimetric method with Periodic Acid Schiff (PAS) Staining of sigma mucin type I was used for microparticles mucoadhesion analysis. In liposomal formulations, 23% mucoadhesion was observed after 6 hours at pH 1.3 (Figure 1a) and 59% mucoadhesion after 6 hours was detected at pH 4.5 (Figure 1b). In the case of microparticles, concentration of cross linking agent (glutaraldehyde, GTA) used was also a determining factor of mucoadhesion in addition to the pH effect. Increase in the concentration of glutaraldehyde have negative impact on mucoadsorption however, increase in pH increase mucoadhesion and vice versa (Figure 2).
Anton Aleksashkin
Lomonosov Moscow State University, Russia
Title: NanoZYME technique applied to antioxidant enzyme, SOD, has high potential in the treatment of diseases related to oxidative stress
Time : 14:55-15:10
Biography:
Anton Aleksashkin has completed his Master’s degree from Lomonosov Moscow State University (MSU). He is a PhD student of Lomonosov MSU in the Faculty of Chemistry and a research fellow in BIND RUS.
Abstract:
Numerous diseases ranging from neurodegenerative to some types of cancers are associated with overproduction of reactive oxygen species. Injection of antioxidants could decrease oxidative stress. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, are the most effective antioxidants in nature and could be used to slow oxidative stress. Unfortunately, injection of native enzymes is not effective due to their rapid elimination and instability in blood. Nanoparticles called “nanozymes” based on block-ionomer complexes of negatively charged proteins with positively charged block-copolymers (in particular, polylysine-polyethyleneglycole, PLL-PEG) were previously developed to encapsulate SOD. These cross-linked particles – nanozymes-1 have nanoscale size and preserve specific activity. However, fast release of enzyme from complexes leads to fast elimination from the body. In this presentation, novel type of nanozymes-2 will be discussed. Second negatively charged block-copolymer (poly(glutamic acid)-polyethyleneglycole (PGlu-PEG) was used, and protamine was used instead of PLL-PEG. We were able to increase the reaction yield from 5% to 45%. Developed particles have neutral charge, 50 nm hydrodynamic diameter while nanozymes-1 have slightly positive charge and 40 nm hydrodynamic diameter. Pharmacokinetic experiments showed remarkably increased T1/2 and AUC of double nanozymes versus both standard nanozymes and native SOD. To evaluate therapeutic efficiency of nanozymes, rat spinal cord injury model was used. Recovery of rats was investigated with MRI imaging and BBB-test. Animals that were injected with nanozymes-2, had significant higher scores in BBB-test and lower volume of damage. Thus, easy, scalable method to encapsulate antioxidant enzyme, SOD, was developed.
Gino Karlo L. Delos Reyes
Northeastern University, USA
Title: Utilizing rosette nanotubes for the delivery of siRNA for cancer therapeutics
Time : 14:55-15:10
Biography:
Gino Karlo L. Delos Reyes is a second year Chemical Engineering PhD student in Dr. Fenniri’s Supramolcular Nanomaterials Lab at Northeastern University. Gino Karlo studies how novel Rosette Nanotubes can be used as targeted drug delivery agents, especially its applications in cancer. He completed his undergraduate degree at the University of California, San Diego where he received a double major in Chemical Engineering and Biochemistry/Cellular Biology.
Abstract:
Rosette Nanotubes (RNTs), a self-assembled supramolecular nanomolecule composed of fused guanine-cytosine (G^C) bases, provide a novel and innovative modality for the delivery of gene therapeutics to target cells with high efficacy1. This study aims at utilizing RNTs as a nanocarrier platform for the delivery of small interfering RNA (siRNA) to knockdown oncogenic genes to facilitate the elimination of cancer from the body. By conjugating positively charged lysine functional groups to the surface of the RNTs, the nanotubes gain the ability to complex negatively charged siRNA through electrostatic interactions. Through specialized FRET-labeled siRNA and gel retardation assay, we have shown that cationic charges on the RNTs strongly affect the binding interaction and the intracellular delivery of the RNT-siRNA nanocomplex. Furthermore, we have observed higher levels of intracellular siRNA delivery utilizing the RNTs as compared to commercially available Lipofectamine through the use of fluorescently labeled siRNA. Improved gene silencing capabilities were also exhibited compared to commercially available siRNA transfection agents. These data suggest that RNTs has the potential to be both an efficient and biocompatible gene delivery platform.
Heba Mohamed Abd El-Azim
Damanhour University, Egypt
Title: Improvement of delivery and permeation of water-soluble vitamins using liposomal buccal dosage form
Time : 15:10-15:25
Biography:
Heba Mohamed Abd El-Azim has completed her M.Sc. degree in pharmaceutics from Faculty of Pharmacy, Alexandria University. She is assistant lecturer of pharmaceutics in the Faculty of Pharmacy, Damanhour University. Her master thesis investigated the role of liposomes as nanocarriers in the transmucosal delivery of water soluble drugs. She has published two posters in international conferences and a research article entitled; “Liposomal buccal mucoadhesive film for improved delivery and permeation of water-soluble vitamins†in the International Journal of Pharmaceutics. She gave about 10 seminars and presentations about nanotechnology and drug delivery systems. She attended 11 national and international conferences.
Abstract:
This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-soluble, low permeable vitamin. Two main strategies were combined; first VB6 was entrapped in liposomes, which were then formulated as mucoadhesive film. Both plain and VB6-loaded liposomes (LPs) containing Lipoid S100 and propylene glycol (~200 nm) were then incorporated into mucoadhesive film composed of SCMC and HPMC. Results showed prolonged release of VB6 (72.65%, T50% diss 105 min) after 6 h from LP-film compared to control film containing free VB6 (96.37%, T50% diss 30 min). Mucoadhesion was assessed both ex vivo on chicken pouch and in vivo in human. Mucoadhesive force of 0.2 N and residence time of 4.4 h were recorded. Ex vivo permeation of VB6, across chicken pouch mucosa indicated increased permeation from LP-systems compared to corresponding controls. Interestingly, incorporation of the vesicles in mucoadhesive film reduced the flux by 36.89% relative to LP-dispersion. Meanwhile, both films provided faster initial permeation than the liquid forms. Correlating the cumulative percent permeated ex vivo with the cumulative percent released in vitro indicated that LPs retarded VB6 release but improved permeation. These promising results represent a step forward in the field of buccal delivery of water- soluble vitamins.
Nada Khudair
Qatar University, Qatar
Title: Non-ionic surfactant vesicles as delivery system for Letrozole
Biography:
Abstract:
Background: Aromatase is an enzyme that leads the bioconversion of androgen into estrogen, which is a main source for cell proliferation and growth in hormone dependent breast cancer. Letrozole (LTZ) is a third generation potent aromatase inhibitor that is approved by the Food and Drug Administration (FDA) for the management of hormone positive breast cancer. The current formulation (Femara®) lacks an effective bioavailability due to LTZ poor-water solubility and rapid systemic metabolism. Aim: To design and characterize LTZ powdered formulations using two formulation approaches; proniosomes and promicelles. Methods: Rotary evaporator apparatus was utilized to produce promicelles. A total of four formulations were prepared, each with a different drug to surfactant ratio. The formulations were prepared by slurry technique and loaded with LTZ. LTZ promicelles and the generated micelles were characterized using zetasizer, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and ultra-performance liquid chromatography (UPLC). Results: Formulation (3) and (4) loaded with 20% LTZ (w/w) were found to be promising with a particle size of 7466±1145 nm and 8543±915 nm, respectively. The drug content was analyzed through UPLC and was found to be 93.45% and 74%, respectively. LTZ entrapment efficiency was reported highest in formulation (4) with a value of 97.5%. Finally, the images obtained from TEM revealed spherical micelles that were in the micro size, confirming the data from the zetasizer. Conclusion: The promicelles were successfully designed and characterized. Particles were spherical and in the micro size with a high entrapment efficiency, indicating improved physicochemical properties of LTZ.
- Track 4: Drug Targeting
Location: Melia Avenida America
Chair
Volkmar Weissig
Midwestern University, USA
Co-Chair
Osama Ibrahim
Bio Innovation, USA
Session Introduction
Osama Ibrahim
Bio Innovation, USA
Title: The history of bioprocess technology in drug discovery and its future perspectives
Time : 17:05-17:25
Biography:
Osama O Ibrahim is a highly-experienced Principle Research Scientist with particular expertise in the fields of biochemistry, microbiology, molecular biology, and bioprocessing for both pharmaceutical and food ingredients. He was External Research Liaison for Kraft Foods with Universities for research projects related to bioprocessing and molecular biology. In the 2005, he accepted an early retirement offer from Kraft Foods and formed his own biotechnology company (Bio Innovation) providing technical and marketing consultation for new start-up biotechnology and food companies. He holds three bioprocessing patents and received his PhD in basic medical science (Microbiology, Immunology and Molecular biology) from New York Medical College. He is a Member of American Chemical Society, American Society of Microbiology, and Society of Industrial Microbiology since 1979.
Abstract:
Bioprocess technology encompasses all of the basic and applied sciences in microbiology, biochemistry and molecular biology as well as the engineering aspects to fully exploit living systems and bring their products to the market place. To-day bioprocesses have become widely used in several fields of commercial biotechnology including in medicines and drug discovery. While our understanding of biotechnological process has rapidly and remarkably advanced in recent years, it has been in existence since prehistoric times, making it one of the oldest technology even before the discovery of the field of microbiology. The discovery of microbial enzymes and the development of bioconversion technology led to the production of new drug with high yields and cost effective. Bioconversion process is also known by the name biotransformation and refers to the use of living organisms or its extracted enzymes to carry out chemical reactions that are not feasible or costly when produced by synthetic chemistry methods. These enzymes convert a substance to a chemically modified form with multiple uses and applications including medicines. In the 1980s, the recombinant gene technology led to the production of genetically engineered insulin for diabetes as the first product manufactured with recombinant technology. This newly developed genetic engineering technology has led to the introduction of a large number of new bio drugs such as interferon, tissue plasmogen activator, erythropoietin, colony-stimulating factors, and monoclonal-antibodies.
Peter Krajcsi
Solvo Biotechnology, Hungary
Title: Role of transporters in permeability of drugs – options for testing, modulation and targeting
Biography:
Peter Krajcsi received his PhD in Medical Biology from the University in Szeged. He is currenty the Chief Scientific Officer of Solvo Biotechnology a manufacturer and service provider in the field of pharmaceutical and nutraceutical applications of membrane transporter technologies. He has published more than 75 papers in reputed journals and has been serving as an editorial board member of three journals.
Abstract:
Physiological cellular barriers of pharmaceutical importance express a large number of membrane transporters. Most membrane transporters either catalyze cellular influx or cellular efflux but some are bidirectional. The role of membrane transporters in modulation of permeability is increasingly recognized and is particularly critical for BCS / BDDCS Clas II-IV drugs. There is a significant cross-talk between transporters and enzymes of xenobiotic metabolism. The two systems may play complementary or compensatory roles. A number of assay systems are available to study transporter – drug interactions as well as transporter mediated drug – drug interactions (tDDI). Cellular assays as well as membrane assays are available. It is important that the expression systems used in transfectants mimic the physiological membrane environment. Physicochemical properties of drugs are important determinants of assay selections as transcellular transport assays (monolayer assays) may work even for intermediate-to- high passive permeability drugs but may not work for very low passive permeability drugs. In contrast, membane uptake assays are ideal for low passive permeability substrates. Apically located intestinal efflux transporters (e.g. P-gp, BCRP) may limit absorption of substrate drugs. Inhibition of the efflux transporters by excipients my increase absorption, bioavailability. Targeting influx transporters may increase absorption and may play a role in tissue targeting too. Importantly, low influx transporter expression in target cells / tissue may lead to resistance to substrate drugs. Exploratory strategies to target influx transporters expressed in the blood – brain barrier have been described.
Tatiana Hurtado de Mendoza
Sanford Burnham Prebys Medical Discovery Institute, USA
Title: iRGD, a tumor-penetrating peptide for tumor-specific drug delivery
Time : 17:25-17:45
Biography:
Tatiana Hurtado de Mendoza completed her Bachelor’s degree in Biochemistry and Molecular Biology at Universidad Autonoma de Madrid, Spain and then moved to San Diego to pursue a PhD in Biology from UCSD/Salk Institute. Currently, she is a Postdoctoral fellow at Sanford Burnham Prebys Medical Discovery Institute
Abstract:
Delivering cancer drugs specifically to tumors and deep into tumor tissue against the high interstitial pressure is a major hurdle in cancer therapy. The iRGD drug delivery system may provide a solution. The iRGD peptide (CRGDK/RGPD/EC) was identified by phage display against metastatic prostate cancers (Sugahara et al, Cancer Cell, 2009). iRGD carries a tumor-specific RGD motif, which recognizes av integrins that are highly expressed on tumor vasculature and tumor cells, and an RXXK/R CendR motif, which binds to a tissue-penetration receptor neuropilin-1. Importantly, the tissue penetration pathway involves an energy-dependent active transport system, which relies on a mechanism similar to macropinocytosis (Pang et al, Nature Communications, 2014). This unique property allows iRGD to accomplish tumor-penetrating delivery of drugs by simple co-administration (Sugahara et al, Science, 2010). Thus, the therapeutic index of various drugs can be enhanced without any chemical modification of the drugs. In fact, iRGD enhanced tumor-specific accumulation and anti-tumor effects of various types of systemic drugs including small chemicals, nanodrugs, and antibodies in a number of tumor types. Our recent studies have revealed that iRGD alone has anti-metastatic effects when delivered intravenously, providing an additional benefit of using the iRGD system for cancer therapy (Sugahara et al, Molecular Cancer Therapy, 2015). In addition, the iRGD co-administration system is effective not only for systemic cancer therapy, but also for intraperitoneal chemotherapy for peritoneal carcinomatosis (Sugahara et al, Journal of Controlled Release, 2015). A brief overview and recent advances of the iRGD system will be discussed at the meeting
Ruchi Bansal
University of Twente, Netherlands
Title: Cell-selective delivery of Interferon gamma peptidomimetic inhibits chronic liver fibrosis and tumor angiogenesis In vivo
Time : 17:45-18:05
Biography:
Ruchi Bansal has completed her PhD (funded by Ubbo Emmius International fellowship) in 2012 from University of Groningen, The Netherlands. In 2011, she received EASL Sheila Sherlock research fellowship (European Association for the Study of the Liver), and The Ruth and Richard Julin’s Foundation Swedish research grant for her postdoctoral research at Karolinska Institute. In 2014, she received prestigious VENI Innovation grant (ZonMw, The Netherlands Organisation for Scientific Research (NWO)) to pursue liver-targeted research in MIRA institute, University of Twente, The Netherlands. She has published more than 15 papers in highly reputed journals and received several young investigator awards.
Abstract:
To date, no pharmacotherapy is available for liver fibrosis. Activated hepatic stellate cells or myofibroblasts are the key extracellular matrix producing effector cells. Thus, pharmacological inhibition of these cells might lead to an effective therapeutic therapy for liver fibrosis. Interferon gamma (IFNγ) is highly potent anti-fibrotic cytokine but it failed in clinical trials due to reduced efficacy and severe adverse effects. Here, we employed an IFNγ peptidomimetic (mimIFNγ) that lacks the extracellular receptor recognition sequence but retains the agonistic activities of IFNγ. Since platelet-derived growth factor receptor beta (PDGFβR) expression is highly over-expressed on key pathogenic cells, we conjugated mimIFNγ to a bicyclic PDGFβR-binding peptide (BiPPB) for selective delivery. The synthesized targeted IFNγ peptidomimetic (mimγ-BiPPB) was extensively investigated for anti-fibrotic and adverse effects in acute or chronic CCl4-induced liver fibrosis mouse models. Furthermore, the construct was investigated for anti-angiogenic and anti-tumor effects in C26-colon carcinoma mouse model. The targeted mimγ-BiPPB construct markedly inhibited early and established hepatic fibrosis in mice. Native IFNγ induced only moderate reduction in fibrosis, while untargeted mimIFNγ and BiPPB had no effect. In addition, untargeted IFNγ significantly induced systemic inflammation and MHC-II expression in brain while mimγ-BiPPB did not induce off-target effects. Furthermore, in C26-colon carcinoma tumor-bearing mice, mimg-BiPPB exhibited significant reduction in tumor angiogenesis and size, whereas other treatments showed no effect. The present study demonstrates the beneficial effects of cell-specific targeting of IFNg peptidomimetic to the disease-inducing cells and therefore represents a highly potential therapeutic approach to treat chronic diseases.
Nermin Salah Ahmed
University in Cairo, Egypt
Title: Design and synthesis of novel non CYP 2D6 mediated tamoxifen analogues
Time : 18:05-18:25
Biography:
Nermin Ahmed has completed her PhD at the German University in Cairo. She is a lecturer of Pharmaceutical Chemistry. She has published about 10 papers in international journals, she has earned a grant of 50000 Euros to satrt a research group in the field of TAM analogues and personalized medecine. She is also a TechWomen delegate working in increasing the girl’s interest in STEM. She is a DAAD Alumni and USA government Alumni as well. She works on promoting enterpreneurship among University students.
Abstract:
Tamoxifen (TAM) is a widely used drug in the prophylaxis and treatment of breast cancer. TAM is metabolized to the more active 4-hydroxytamoxifen (4-OH-TAM) and endoxifen by cytochrome P450 (CYP) mainly CYP2D6 and CYP3A4 enzymes. Due to the genetic polymorphisms in CYP2D6 genes, high variation in the clinical outcomes of TAM treatment is observed among women of different populations. To address this issue, novel TAM analogues with possible altered activation pathways were synthesized. These analogues were tested for their antiproliferative action on MCF-7 breast cancer cell lines as well as their binding affinity for estrogen receptor (ER) ER-α and ER-β receptors. These entire novel compounds showed better antiproliferative activity than did TAM on the MCF-7 cells. Moreover, compound 1 exhibited a half maximal growth inhibition (GI50) that was 1000 times more potent than that of TAM (GI50 <0.005µM vs 1.58 µM, respectively). Along with a broad spectrum activity on various cancer cell lines, all the TAM analogues showed considerable activity on the ER-negative breast cancer cell line. For further study, compound 2 was incubated in human liver microsomes (HLM), human hepatocytes (hHEP) and CYP2D6 supersomes. The active hydroxyl metabolite was detected after incubation in HLM only, implicating the involvement of other enzymes in its metabolism. These results prove that this novel series of TAM analogues might provide improved clinical outcomes for poor 2D6 metabolizers.
Yousef Alomi
Ministry of Health, KSA
Title: Looking to the future: Clinical pharmacy services in Saudi Arabia
Time : 15:30-15:50
Biography:
Dr. Yousef Alomi, Head of General Administration of Pharmaceutical Care Administration, and Head of National Drug Information Center, MOH Saudi Arabia Dr. Alomi is a product of King Saud University confirmed with the degree of Bachelor of Pharmaceutical Sciences in the year 1992. After six-years of higher study, he earned his Master of Clinical Pharmacy from the same university in the 1998. He is an affiliated clinical instructor of Purdue University in the USA. He is adjunct assistant professor of King Saud University college of Pharmacy. Dr. Alomi worked as clinical pharmacist in critical care area and nutrition support. He is He is establish and implement several programs at MOH Hospitals at first time; Clinical Pharmacy Program, Medication Safety Program, Pain Management Program, Anticoagulation Program and Pharmacy Infection Control, including 30 Adult and 20 Pediatrics Clinical Pharmacy Program; he founder of Mass Gathering Pharmaceutical Care in Saudi Arabia. He became a member of advisory board of the Arab Pharmaceutical Journal in 2010. He became as Pharmacy Board Member of Saudi Commission of Health Care Specialities2010-2013. He had several research papers in clinical Pharmacy and Pharmacy practice published in ACCP and ISPOR conferences; He had several presentations in the clinical pharmacy and pharmacy practice at several conferences in and outside Saudi Arabia.
Abstract:
Clinical pharmacy services had been started since 1980s with small department of clinical pharmacy at college of pharmacy, and three specialized, University, and Ministry of Health hospitals. Over more than 40 years, it expanded to more than 20 colleges of pharmacy where almost a total of 300 clinical pharmacists graduate per a year. More than 50 MOH, Universities, and specialized hospitals apply clinical pharmacy services with different in the size and depth of the services. More than 30 clinical pharmacy programs offer through hospitals and some organized by MOH general administration of pharmaceutical care for adults and pediatrics patients. Those programs are but not limited to critical care pharmacy program, pediatrics pharmacy program, pain management program, antimicrobial stewardship program, anticoagulation program, cardiology pharmacy program, etc. Pharmacy practice residency post graduate year one (PGY1), PGY2, and recently specialized residency PGY3 in the cardiology and infectious is currently applying now. In addition, hotline calling services of national drug information 24/7 days is providing to public and professional. Clinical pharmacy services is changing quickly over the last years in Saudi Arabia leading to improve patient outcomes, prevent drug related problems and reduce unnecessary cost.
- Track 11: Medical Devices for Drug Delivery
Location: Melia Avenida America
- Track 2: Formulation Aspects for Various Routes
Location: Melia Avenida America
Session Introduction
Yehia Ismail Khalil
University of Bhagdad, Iran
Title: Formulation and evaluation of zolmitriptan bilayer oral strip
Biography:
Abstract:
Oral strip is one of acceptable and palatable delivery system assist patients in any age to be easily administered. Zolmitriptan is a 5HT receptor agonist used to relief migraine attack was studied to formulate it as a bilayer oral strip, both layers disintegrate within seconds but each layer has its own drug release (the first layer formulate to release drug rapidly while the second layer release its drug in a sustained release manner) the first release to get rapid mask the migraine attack and the second release to prevent recurrent attack for certain time period, this strip formulated by casting and spraying techniques to get bilayer film with sufficient physical and mechanical properties using different hydrophilic and hydrophobic polymers with different plasticizers in different ratios and concentrations and study their effects on the in vitro disintegration time, the mechanical properties of the film and also the in vitro release profile, other studied parameters such as drug-excipients compatibility were evaluated. The disintegration time of the optimized formula (Fx10) was 32 sec, release of 50% of the drug within first 15 minutes and the remaining drug released as sustained reach to 4 hours were seen. The fast release profile was compared with the marketed zolmitriptan oral dispersible tablet. FTIR and DSC thermogram studies indicate no presence of incompatibility with the excipients either during mixing or during casting.
- Track 6: Application of Nanotechnology
Location: Melia Avenida America
- Track 12: Smart Drug Delivery Systems
Location: Melia Avenida America
- Young Researcher Forum
Location: Melia Avenida America
- Track 10: Biotherapeutics-Drug Discovery and Development
Location: Melia Avenida America
- Poster Presentations 16:00-18:00 @ Salamanca
Location: Melia Avenida America
- Track 7: Major Challenges in Drug Delivery System
Location: Melia Avenida America
- Track 8: Physiological Considerations
Location: Melia Avenida America
Session Introduction
Thawatchai Phaechamud
Silpakorn University, Thailand
Title: Solvent exchange-induced in situ forming gel comprising eudragit RS-antimicrobial drugs
Biography:
Thawatchai Phaechamud has completed his PhD from Chulalongkorn University. He has published more than 20 papers in pharmaceutical journals and has been serving as an Editorial Board Member of pharmaceutical science of country
Abstract:
Eudragit RS (ERS), a quaternary polyacrylate positively charged polymer, exhibits a very low permeability and swells in aqueous media independently of pH without dissolving. Owing to its high solubility in N-methyl pyrrolidone (NMP) it was interesting to apply as polymer matrix for solvent-exchanged in situ forming gel which this drug delivery system was in sol form and transforming into solid-like after injection and exposure to the aqueous fluid of the body. The aim of this research was to study the parameters affecting the gel properties, drug release and antimicrobial activities of the in situ forming gels prepared from Eudragit RS dissolved in NMP to deliver the antimicrobial agents (doxycycline hyclate, metronidazole and benzyl peroxide) for periodontitis treatment. The solvent exchange between NMP and an external aqueous simulated gingival crevicular fluid stimulated the dissolved Eudragit RS transforming into the opaque rigid gel. Doxycycline hyclate, metronidazole and benzyl peroxide loaded-ERS systems exhibited Newtonian flow which their syringeabilities were acceptable. The higher-loaded Eudragit RS promoted the more prolongation of drug release because of the retardation of water diffusion into the precipitated matrix. Antimicrobial activities against Staphylococcus aureus, Escherichia coli, Candida albicans, Streptococcus mutans and Porphyrommonas gingivalis depended on type of drugs and test microorganisms. Doxycycline hyclate loaded-Eudragit RS systems showed these activities greater than the others however all of them could inhibit the all test microorganisms. Thus the solvent exchange-induced in situ forming gels comprising Eudragit RS-antimicrobial drugs exhibited potential use as localized delivery systems for periodontitis treatment
Hervé Hillaireau
Université Paris-Sud, France
Title: Drug delivery strategies aimed at improving bioavailability and bio-distribution of anti-HIV chemotherapy
Biography:
Hervé Hillaireau is Assistant Professor in Pharmaceutical Technology at the School of Pharmacy of Université Paris-Sud. His research at Institut Galien Paris-Sud in Elias Fattal’s group relates to the design and the toxicological evaluation of biodegradable nanoparticles as drug nano-carriers, with a focus on surface functionalization and encapsulation of nucleic acids, peptides and nucleotide/nucleoside analogues, applied to anti-cancer and anti-viral therapies. He holds a Chemical Engineer Degree from Chimie ParisTech with a PhD in Pharmaceutical Technology (2006) and was previously Post-Doc at Harvard University. He has published around 35 papers in international peer-reviewed journals and book chapters.
Abstract:
In the context of the treatment of HIV/AIDS, many improvements have been achieved since the introduction of the combination therapy (HAART). Nevertheless, no cure for this disease has been so far possible, because of some particular features of the chemotherapies. The first main concern is the poor drug bioavailability, resulting in repeated administrations and therefore a demanding compliance. A second important challenge is the need to target the drugs into the so-called reservoirs and sanctuaries, i.e., cells or body compartments where drugs cannot penetrate or are distributed in sub-active concentrations. The lack of antiviral action in these regions allows the virus to lie latent and start to replicate at any moment after therapy suspension. Recent drug delivery strategies addressing these two limitations will be discussed: (i) strategies aimed at improving the bioavailability by increasing either the drug absorption or the passage of the target cell membrane, and/or by extending the efficacy time of drugs; (ii) strategies aimed at improving the bio-distribution by targeting the drugs to the reservoirs and the sanctuaries, in particular the mononuclear phagocyte system and the brain.
Biography:
Asha Patel has 5.4 years of teaching and PG research experience at Anand Pharmacy College, Anand in the discipline of Pharmaceutics and Novel Drug Delivery System. Asha holds a Bachelor’s degree from Maliba Pharmacy College, Surat and PG studies in Pharmaceutics from Sardar Patel University, V.V. Nagar, Gujarat. She has completed her PhD research project on nanoemulsion as drug delivery tool for bioavailability enhancement at Dharmsinh Desai University, Nadiad. Additionally Asha has two years of industrial experience in R & D laboratory at Pharmanza Herbal Pvt. Ltd. Asha has area of expertise in Development and Characterization of Nano-colloidal 9nanomicelles, niosomes, polymeric nanoparticles, nanosuspension for oral, ocular, topical drug delivery system for therapeutic application. Asha had presented more than 10 Research paper in various International and National conferences held in India. She has published more than 5 research papers in peer reviewed journals. Asha had delivered a training session on Optimization of Nanoemulsion mixtures through Design of Experimentation and use of Chemometric tools in four day QbD and DoE certification course held at Anand Pharmacy College, Anand.
Abstract:
The current studies entail systematic development, optimization and evaluation (in vitro, ex-vivo and in vivo) of the nanoemulsion based formulation employing rationale of formulation by design (FbD) and multivariate mathematical modelling approach to improve the solubility and in turn bioavailability for enhancing permeation of Boswellic acids in skin layers. Nanoemulsion system comprising of Isopropyl myristate (oily solubilizer), Tween 80 (surfactant) and Transcutol P (co-surfactant) was developed using Simplex lattice mixture experimental design to optimize mixture components effect on critical responses (viz. Y1 Droplet size and Y2 In- vitro cumulative drug permeation). Partial least square regression analysis operates through Excel STAT to influence collinearity of mixture composition on permeation behavior of drug from the nanoemulsion. The size of droplets and permeability coefficients showed good correlation by partial least square regression plots. TEM study confirmed morphological behavior of nanodroplets. The promising nanoemulsion was incorporated into hydrogel using Carbopol 940 for ease of topical application. The optimized formulation was assessed for in-vitro permeation study using dialysis membrane and ex vivo skin permeation using rat abdominal skin. About 3.25 fold increase in flux was seen with nanoemulsion, while nanogel showed 1.45 fold increase in flux compared to carbopol gel with enhancement ratio 4.57 and 1.59 respectively. The permeation data analysis corroborated greater drug permeation and in vivo pharmacodynamic study through Carrageenan induced rat paw edema model demonstrated a pronounced anti-inflammatory effect. Our study illustrated scientific and statistical evidence for potential of developed nanoemulsion with improved biopharmaceutics performance as possible alternative to traditional topical formulations.