Day 2 :
Keynote Forum
Joel Richard
IPSEN, France
Keynote: Oral peptide delivery: How to address the challenges of peptide stability in the GI tract and oral bioavailability
Time : 09:30 - 09:55
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?
Keynote Forum
Kang Choon Lee
SungKyunKwan University, South Korea
Keynote: Strategic PEGylation: Half-life extension of biologic drugs
Time : 09:55 - 10:20
Biography:
Dr. Kang Choon Lee is Haengdan Distinguished Professor at College 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. For the clinically translating and commercializing site-specific engineered peptide/protein drugs developed by his laboratory, he founded D&D PharmaTech, Korea and also co-founded and serves as a Board Member of Theraly Pharmaceuticals, USA.
Abstract:
The tremendous potential of biologic drugs is hampered by short half-lives in vivo, resulting in significantly lower potency than activity seen in vitro. These short-acting therapeutic agents require frequent dosing profiles that can reduce applicability to the clinic, particularly for chronic conditions. Therefore, half-life extension technologies are entering the clinic to enable improved or new biologic therapies. PEGylation is a commonly utilized technique to improve drug solubility and stability, prolong blood circulation time, reduce immunogenicity, and decrease dosing frequency. As with any form of molecular modification, the active site is affected and can drastically decrease the bioactivity of the therapeutic agent, especially when the modification is performed on a small molecular weight molecule like peptides and small proteins. Steric hindrance from high molecular weight PEG can lead to a dramatic loss in the biological and pharmacological activity of the molecules. The higher the molecular weight, the lower the bioactivity. Therefore, it is generally accepted that a balance must be struck between the molecular weight of the PEG and the activity of the therapeutic molecule to reach sufficient drug efficacy. The strategic PEGylation technique introduced here offers many benefits over the conventional PEGylated forms of peptides and proteins. Strategic PEGylation signifies that a tradeoff of PEGylation for bioactivity is not necessary. Specifically, this abstract focuses on the strategic PEGylation of potent therapeutic peptides for GLP-1 analogues as a model peptide. Strategic PEGylation can be a platform technology to extend the half-life while preserving the biological activity of peptide and small protein drugs.
- 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:
NA
Abstract:
NA
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.
Ahmed Mahmoud Abdelhaleem Ali
Beni Suef University, Egypt
Title: Quetiapine-nicotinamide co-amorphous dispersion: A new strategy for improving physicochemical properties and ex-vivo performance of a model antipsychotic drug
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 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:
NA
Abstract:
NA
Joel Richard
IPSEN, France
Title: Oral peptide delivery: How to address the challenges of peptide stability in the GI tract and oral bioavailability
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.
- 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.
- Poster Presentations 16:00-18:00 @ Salamanca