Day 1 :
Keynote Forum
Volkmar Weissig
Midwestern University College of Pharmacy Glendale, USA
Keynote: Pharmaceuticial Nanocarriers: Past / Present / Future
Time : 09:30 - 09:55
Biography:
Volkmar Weissig, Sc.D., Ph.D. 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). Dr. Weissig holds 16 patents and he has published 98 research papers, review articles and book chapters. He also edited and published 8 books. 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:
About fifteen years ago, the National Institute of Health (USA) launched the National Nanotechnology Initiative to support, coordinate, and advance research and development of nanoscale projects. The impact of this new program on health-science related research and development became quickly visible. Broad governmental financial support advanced the start of new, and the deepening of already existing, interdisciplinary research. The anticipated merger of nanoscience with medicine quickly instigated the conceptualization of nanomedicine. The adoption of nanoscience terminology by pharmaceutical scientists resulted in the advent of nanopharmaceuticals. The term "nano" became tantamount to "cutting-edge" and was quickly embraced by the pharmaceutical science community. Colloidal drug delivery systems reemerged as nanodrug delivery systems; colloidal gold became a suspension of nano gold particles. In this presentation I shall review nanoscience related definitions applied to pharmaceuticals, discuss currently approved drug formulations which are publicized as nanopharmaceuticals and briefly review currently ongoing clinical trials within the broad field of nanomedicine. When confining the definition of nanopharmaceuticals to therapeutic formulations, in which the unique physicochemical properties expressed in the nanosize range, when man-made, play the pivotal therapeutic role, I shall argue that the current number of clincial trials neither reflects the massive investments made in the field of nanomedicine nor the general hype associated with the term "nano." However, I shall also emphasize the tremendous efforts currently underway worldwide, at the bench and in preclinical research, in order to make the big promise of the nano revolution a reality.
Keynote Forum
Peter Krajcsi
Solvo Biotechnology, Hungary
Keynote: Role of transporters in permeability of drugs – options for testing, modulation and targeting
Time : 09:55 - 10:20
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 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.
Keynote Forum
Felix Kratz
CytRx Corporation, Germany
Keynote: Albumin-binding drugs as drug delivery systems in oncology
Time : 10:35-11:00
Biography:
Felix Kratz is a medicinal chemist with more than 25 years of pertinent experience in the preclinical development of anticancer drugs, prodrugs and protein conjugation chemistry and has profound knowledge of translational research from the laboratory to the clinic. He has successfully transferred aldoxorubicin, CytRx clinical lead compound, from bench to bedside that is based on an innovative drug delivery platform exploiting circulating albumin as a tumor-specific drug carrier. He has authored approximately 260 scientific publications, book articles and proceedings and is the inventor of over 20 patents and patent applications. As Vice President he heads the CytRx Drug Discovery Branch located in the Innovation Center Freiburg, Germany.
Abstract:
Albumin is playing an increasing role as a drug carrier in cancer therapy considering that numerous preclinical studies demonstrate an accumulation of albumin in experimental solid tumors. Principally, anticancer prodrugs can be covalently bound to exogenous or endogenous albumin, or antitumor agents are physically adsorbed to albumin forming nanoparticles as a galenic formulation. Clinically, the most advanced drug delivery system is an albumin-based nanoparticle with paclitacel (Abraxane®) approved for the treatment of metastatic breast cancer, pancreatic cancer and NSCLC. An alternative to physically adsorbing drugs is to attach the latter covalently to albumin. Aldoxorubicin, an albumin-binding drug of doxorubicin with acid-sensitive properties, that has reached an advanced stage of clinical development with results from a registrational phase III trial against second-line soft-tissue sarcoma expected in Q2 2016. The underlying drug delivery strategy is a platform technology based on two features: (a) in situ binding of the prodrug to the cysteine-34 position of endogenous albumin after intravenous administration due to a thiol-reactive maleimide group in the molecule; (b) release of albumin-bound drug at the tumor site due to the incorporation of an acid-sensitive cleavable bond between the drug and the carrier. The acid-sensitive linker contains a hydrazone bond, and CytRx have developed a broad spectrum of linkers based on this release mechanism (LADRTM – linker activated drug release technology) that have resulted in promising albumin-binding drugs in preclinical setting.
Keynote Forum
Amiram Goldblum
The Hebrew University of Jerusalem, Israel
Keynote: Computer-aided design of liposomal drugs: In silico prediction and experimental validation of drug candidates
Time : 11:00 - 11:25
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.
- 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.
Ehsan Shamaeli
Tarbiat Modares University, Iran
Title: Nanobiocomposite for dual stimuli-responsive smart release of insulin using a novel high effective surface area functionalized gold nanoparticle-polypyrrole
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 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.