Day 1 :
Keynote Forum
R N Saha
BITS Pilani, Dubai Campus, UAE
Keynote: Nanoparticulate drug delivery systems for modifi ed tissue distribution and better cancer chemotherapy
Time : 10:05 - 10:30
Biography:
R N Saha is Shri B K Birla & Shrimati Sarala Birla, Chair Professor (Senior Professor of Pharmacy) and Director of BITS Pilani Dubai Campus. In 2011 he has been awarded Shri B K Birla and Shrimati Sarala Birla Chair Professorship at BITS Pilani for contributions in teaching and research. He has vast experience in the field of Pharmacy especially in Pharmaceutics, novel drug delivery systems and Pharmacokinetics. He received “Pharmacy Professional of the Year 2013” Award given by Indian Association of Pharmaceutical Scientists and Technologists. He is also recipient of “The Best Pharmacy Teacher Award” for the year 2005, awarded by the Association of Pharmaceuticals Teachers if India (APTI), in recognition of his contribution in teaching and research in the fi eld of Pharmacy. He is also member of many scientific associations and societies like Association of Pharmaceutical Teachers of India (APTI); Indian Pharmaceutical Association (IPA); Indian Society of Technical Education (ISTE); Controlled Release Society Inc., USA; American Association of Pharmaceutical Scientists (AAPS), USA; American Chemical Society, USA; Controlled Release Society, Indian Chapter.
Abstract:
New insight of diseases and pharmacokinetic information have made drug deliver totally different. It is no more just delivery of drugs, as objectives are totally different. Present approaches of design of delivery systems are more challenging and expectations are much higher. Non-selective distribution of drugs from conventional deliver systems makes dose requirement high and lead to severe side effects or toxic effects, especially in cancer chemotherapy and CNS treatment. Application of nanotechnology in drug delivery, can make modified/selective distribution, decreased dose, lesser or no side effects and better therapy. Recent studies indicated selective or modified distribution, enhanced pharmacokinetic properties and better therapeutic efficacy for nanoparticulate delivery systems of selected anticancer drugs. In vivo study of liver carcinoma therapy in animal indicated highly encouraging effi cacy with enhanced overall survival when treated with nanoparticulate systems
Keynote Forum
Alex Nivorozhkin
Neo-Advent Technologies LLC., USA
Keynote: Silica-based matrixes for drug delivery: Ready for a prime time?
Time : 10:30 - 10:35
Biography:
Nivorozhkin is an entrepreneur and a team builder in life sciences’ arena with vast experience and track record in an early technology transfer and development. He was a co-founding member of Boston BioCom, LLC, a biopharma company funded by the seed investment from Pfizer. Alex gained substantial experience in the commercial aspects of drug discovery and development at Epix Medical and Inotek Pharmaceuticals where he served as the company’s Head of Medicinal Chemistry. He served as a Senior Program Manager at the Center of Integration of Medicine and Innovative Technologies (CIMIT) at Massachusetts General Hospital, a consortium of the Harvard Medical School-affi liated hospitals, Boston University, Draper Laboratory and MIT aimed at developing new medical devices; and a Scientific Programs Officer at Sheldon and Miriam Adelson Medical Research Foundation. He is a co-inventor of several drug candidates that have advanced to clinical trials and late pre-clinical studies in the United States, has co-authored over 60 scientific publications in different areas of chemistry, chemical biology, and material sciences and holds more than 20 patents. Alex received a Ph D in Physical Organic Chemistry from Rostov University and conducted the postdoctoral research at the University Paris-Sud, France, and the Department of Chemistry and Chemical Biology, Harvard University, Cambridge.
Abstract:
Sol-gel-derived and silica-containing materials have made signifi cant strides into the material sciences’ applications and established presence in multiple commercial products and industrial technologies. In biomedical field, extensive research indicated their potential utility in areas such as enzyme and live-cell encapsulation. These materials hold promise in a drug delivery area as well General biocompatibility and biodegradable properties make silicas and sol-gels attractive matrixes. Nanotechnology brings in a possibility for a subtle tune-up of the particles fine structure and variety of functionalization opportunities for covalent and non-covalent binding of the cargo. Th is presentation will review key developments in using silica materials in drug delivery applications and focus on the properties and processes that could be controlling issues in moving early discovery findings into the realm of commercial applications and platform technologies that are compatible with FDA requirements for drug products to enter clinical trials.
Keynote Forum
Khaled Mohamed Hosny
King Abdulaziz University, Kingdom of Saudi Arabia
Keynote: Novel drug delivery systems loaded with bone morphogenetic protein for the repair of alveolar bone defects
Time : 11:10 - 11:35
Biography:
Khaled Hosny is a Associate Professor of Pharmaceutics and Industrial Pharmacy at King Abdulaziz University, Kingdom of Saudi Arabia. He was granted his PhD from Cairo university, Egypt, in 2006. He is currently supervising several PhD and Master degree postgraduate students. Hosny participating in several advanced research projects. His major research interests focused on Novel drug delivery systems. Hosny has a lot of publications in international journals.
Abstract:
Cleft lip and palate is the most common congenital deformities around the world. It is a severe birth defect that affects facial structures, especially maxilla-mandibular structures. Treatment of patients with cleft lip and palate represents a real problem since it requires a comprehensive multidisciplinary approach that involves multiple surgeries and a lengthy orthodontic treatment. An important step in the treatment involves bone grafting of the associated alveolar defects. Bone morphogenetic proteins (BMPs) are members of the transforming growth factors super family that act as osteoinductive factors by inducing the differentiation of osteoblasts from mesenchymal cell. Previous studies have shown the ability of BMPs to induce bone formation in a variety of models having many clinical applications in orthopedics and in oral and maxillofacial surgery. The aim of our studies is to develop and test a new non-invasive injectable graft for the repair of alveolar bone cleft s using recombinant human bone morphogenetic protein-2 (rhBMP-2), encapsulated within injectable vesicular and nanoparticulate drug delivery systems. One of this delivery systems is injectable liposomal in situ gel. Different liposomal formulation loaded with rhBMP-2 were prepared, the effects of method of preparation, and lipid content on encapsulation effi ciency of rhBMP-2 within the liposomes were studied. For the preparation of in situ gel, deacetylated gellan gum was used, the in vitro gelation characteristics of the gel were evaluated. In vivo pharmacokinetic and histology were also assessed. Critical size alveolar defects were surgically created in the maxillae of 30 New Zealand rabbits and were treated by different injectable formulae including rhBMP-2 liposomal in situ gel. The results indicated that the prepared (rhBMP-2) liposomal in situ gel was found to prolong the release and the residence time of BMP-2 within rabbits for more than 7 days. Histomorphometric assessment showed 67% trabecular bone filling of the defects treated by this novel formulation.
Keynote Forum
Peter Karpinski
Novartis Pharmaceuticals Corp., USA
Keynote: Perplex polymorphic behavior of active pharmaceutical ingredients
Time : 11:35 - 12:00
Biography:
Peter Karpinski, recently retired from Novartis Pharmaceuticals, USA, is a consultant, expert witness, and trainer in the areas of polymorphism, form/salt selection, and characterization of APIs; and crystallization & precipitation processes. At Novartis, Karpinski was the leader of Particle Engineering and Salt & Polymorphism nnetworks. Karpinski has over 40 years of international experience in research on crystallization and precipitation processes. He taught chemical engineering at Polish and US universities, published several textbooks and over 50 refereed papers, presented dozens of invited papers at national and international symposia, and holds a number of patents.
Abstract:
Different polymorphs of the same drug substance display distinct physical properties, such as melting point, solubility, dissolution rate, hygroscopicity, stability, etc. The ability to successfully produce and reproduce specific stable polymorphs is intricately correlated with the efficiency and speed of drug development, the robustness of manufacturing process, and ultimately – the stability and quality of active pharmaceutical ingredients (APIs) This paper focuses on several interesting – and sometimes perplex – case study examples of polymorphs ‘behaving badly’. Statistically, 85% APIs exhibit (pseudo) polymorphism, and 50% of APIs have multiple (pseudo) polymorphs. The capability to effectively and consistently manufacture specific stable (pseudo) polymorphs is an integral part of the full API development process. This cannot be accomplished without a thorough and systematic process involving the polymorph discovery stage, polymorph detection, and analytical determination of the properties of the forms discovered. These nontrivial tasks are full of surprises - as in the world of polymorphs confusing results are standard. Challenging and/or unusual situations are common, such as: occurrence of forms difficult to discriminate amongst, forms difficult to detect, ‘disappearing’ polymorphs, isostructural forms of same and diff erent molecules, same form but inconsistent properties for diff erent batches, or a new, more stable form is discovered (too) late… In order to avoid late-stage development surprises, only thermodynamically most stable API forms should be developed. Frequently, such forms are discovered aft er a significant research and development effort. Multiple complementary techniques must be used in polymorph detection and characterization which, however, is a time-consuming and highly labor-intensive exercise.
- Track 3: Recent Technologies in Novel Drug Delivery Systems
Track 4: Nanotechnology in Drug Delivery Systems
Chair
R N Saha
BITS Pilani Dubai Campus, UAE
Co-Chair
Luisa Fiandra
Luigi Sacco University Hospital, Italy
Session Introduction
Vignesh Muthuvijayan
Indian Institute of Technology Madras, India
Title: A novel and simple technique for separation of liposomes from unloaded drug molecules
Time : 12:00 - 12:20
Biography:
Dr. Vignesh Muthuvijayan has completed his PhD from the Department of Chemical Engineering, Oklahoma State University, USA and postdoctoral studies from Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, USA. He is currently working as an Assistant Professor in the Department of Biotechnology, Indian Institute of Technology Madras. His research focuses on developing polymeric materials for biomedical applications such as implants, drug delivery and tissue engineering.
Abstract:
Liposomes have been used in drug delivery for decades. After drug loading, liposomes must be separated from the unloaded drug molecules. Currently, dialysis, density gradient centrifugation, ultracentrifugation and column chromatography are used for separation of liposomes. These techniques are primarily applicable for small-scale production 1. Also, they are tedious and/or expensive. Here, we have developed a rapid and cost-effective method for separation of liposomes from unloaded drug molecules. We prepared phospholipids from egg yolk 2 and prepared the liposomes using previously described techniques 3. We separated the liposomes using precipitation with ethanol, acetone and isopropanol. We optimized the separation process using a 2-factorial design with volume of precipitating agent and time as the input factors and percentage recovery and particle size ratio as the output factors. We considered the points with 100% recovery and particle size ratio of 1 as the optimum points. The studies showed that the volume of precipitating agent used plays a significant role separation of liposomes and not the time of incubation. We also identified that optimum separation was obtained using ethanol and acetone (Figure 1a and 1b). In case of isopropanol, although particle size wasn’t affected, the maximum recovery obtained was less than 60% (Figure 1c). The results show that using ethanol and acetone, we can separate liposomes within 20 minutes with a recovery close to 100% without change in particle size. TEM analysis has to be performed to confirm the results observed. A model drug (Toluidine Blue) was loaded to the separated liposomes and the release was studied (Figure 2). The release profiles were modeled using Higuchi’s equation, Peppas model and saturation kinetics model.
Robert Pola
Institute of Macromolecular Chemistry AS CR, Czech Republic
Title: Polymer drug carriers with enhanced penetration into tumor cells
Time : 12:20 - 12:40
Biography:
Robert Pola has completed his PhD at the age of 29 years from Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic (IMC). He is the member of Department of Biomedicinal Polymers of IMC. He has published 15 papers in reputed international journals.His research focus is based on synthesis of peptide sequences and preparation of water-soluble polymer conjugates used as drug delivery systems for effective treatment of cancer or for vaccination.
Abstract:
Conjugation of anti-tumor drugs to polymer carriers can improve their pharmacological properties. An attached tumor-targeting ligand further increases therapeutic efficiency. Oligopeptides are frequently used as targeting ligands mimicking determinant protein fragments. However, selective delivery to tumor cells is not the only requirement. An enhanced cellular uptake is another key factor for the therapeutic efficiency of the polymeric drugs. This can be mediated by cell-penetrating peptides (CPP) which facilitate the conjugate’s penetration through the cytoplasmic membrane. Yet another key issue is the controlled release of the cargo. We propose a new generation of polymer therapeutics targeted to tumor cells using specific targeting ligands and CPPs. The distinct advantage of this approach is that all components, i.e. drug, targeting ligand (RGD based peptides) and CPP (PFVYLI, R9F2, etc.), are attached to a polymer carrier based on a copolymer of N-(2-hydroxypropyl)-methacrylamide. A cytostatic drug pirarubicin attached to the polymer is inactive during the transport in the blood; once inside the cell it is released and regains its activity. The polymer conjugates with CPP exhibited much higher cell uptake than the control conjugates as shown by FACS and fluorescence confocal microscopy.
Luisa Fiandra
Luigi Sacco University Hospital, Italy
Title: Delivery of nanoformulated Antiretroviral drugs across the blood brain barrier
Time : 12:40 - 13:00
Biography:
Luisa, after a long post-doctoral experience at the University of Milan in the field of transport physiology with a specific competence in permeability processes through intact epithelia and cellular membranes, Dr.Fiandrais nowresearcher in L. Sacco University Hospital of Milan. Her present field of interest is the study of the delivery of nanoformulated in animal models for future application in breast cancer oncology and HIV treatment.From 2010, as scientific coordinator of the NanoMeDia Project, funded by RegioneLombardia (Italy), Dr.Fiandra coordinates the research activity of the Nanomedicine Laboratory of L. Sacco University Hospital, the NanoBioLab of the Department of Biotechnology and Biosciences (University of Milan-Bicocca) and the Center of Electron Microscopy for Nanotechnologies Appllied to Medicine of the Department of Biomedical and Clinical Sciences L. Sacco (University of Milan).
Abstract:
In HIV management, eradication of virus by sanctuary sites remains a main challenge. In fact, although current antiretroviral (ARV) therapies suppress plasma HIV below detectable levels in a consistent proportion of subjects, total virus eradication is still beyond our possibilities. An important barrier to achieve such goal is related to the suboptimal concentrations of ARVs within the HIV sanctuaries. Th e central nervous system (CNS) is a key example of sanctuary where viral replication occurs despite of a complete viral suppression in the peripheral blood. In recent years, nanotechnology has provided great promise in the eradication of HIV from CNS. However, this is the first time in which a complex and heavy peptide like enfuvirtide (Enf), which normally does not penetrate in the CNS, is found to cross the blood brain barrier (BBB) of mice, by conjugation with a nanoconstruct. We demonstrated that iron oxide nanoparticles coated with an amphiphilic polimer (MYTS), labeled with FITC, increased AF660-Enf translocation across BBB in vitro, using a validated BBB model composed of rat BMVECs and astrocytes, and in mice i.v. injected with the nanoformulated Enf. We describe a delivery mechanism involving the uptake of MYTS-Enf in the endothelial cells, the nanocomplex dissociation and the release of the peptide, which is effi ciently excreted into the outside environment (Figure 1). Th e dissociation seems to involve the degradation of the PMA shells bearing the peptide into the more mature endosomal compartments, as an eff ect of the increased acidity and enzymatic activity of their inner environment, to be then completed within lysosomes.
Alena Braunova
Institute of Macromolecular Chemistry AS CR, Czech Republic
Title: Block copolymers of poly(N-2-hydroxypropyl methacrylamide) and poly(propylene glycol)–the way to inhibit P-glycoprotein?
Time : 13:40 - 14:00
Biography:
Alena Braunová has completed her PhD in 2006 from Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic (IMC). She is a member of Department of Biomedicinal Polymers of IMC. She has published 12 papers in reputed international journals, which were cited more than 60 times and she is an author of more than 40 international conference contributions and abstracts.Her research focus is based on preparation of micellar and water-soluble drug delivery systems for effective treatment of cancer and cancerdiagnostics.
Abstract:
Tumour cell resistance tomultiple cytotoxic drugs (multi-drug resistance, MDR), especially to anthracycline antibiotics, is one of the main causes of imperfect efficacy of chemotherapy in current medicine. MDR is a protective response of tumour cells caused by long-term effect of drugs onto the cells. The cells could then decrease the drug intracellular concentration by various mechanisms – e.g. by drug effluxusing special transmembrane proteins, particularly P-glycoprotein (P-gp). P-gp is an ATP-dependent efflux pump of xenobiotic compounds with wide substrate specificity and it is a member of a family of ATP-binding cassette transporters. While in healthy cells P-gp effluxes xenobiotics and toxins, in tumour cells, where P-gp is expressed in much higher amount, contributes P-gp due to this property frequently to MDR. Therefore, P-gp inhibition should cause a better drug penetration into the cells, and thus more effective cancer therapy. Our work is focused on the synthesis of amphiphilic block polymer-drug conjugates, where one block is based on hydrophilic poly(N-2-hydroxypropyl methacrylamide and the other is hydrophobic derivative of poly (propylene glycol), which should be responsible for P-gp inhibition. These blocks form particles due to their different physico-chemical properties and thereby polymer-drug-conjugate molecular weight increase. This fact should be an advantage for passive targeting of these systems preferentially into solid tumours due to the Enhanced Permeability and Retention effect. The drug doxorubicin is bounded to the conjugate by pH-sensitive hydrazone bond, good degradable inside the cells (pH 5.0) but more stable in bloodstream (pH 7.4). Cell viability assay on MDR cancer cell lines are under way.
Tsann-Long Su
Academia Sinica, Taiwan
Title: Early preclinical study of BO-1978 for the treatment of Non-Small Cell Lung Carcinoma (NSCLC), in combination with Gefitinib
Time : 14:00 - 14:20
Biography:
Tsann-Long Su has completed his PhD from the Free University of Berlin, and then worked as a Postdoctoral Fellow at Schering AG, Berlin, Germany. He then moved to the Memorial Sloan-Kettering Cancer Center, New York, USA, and continued his research on developing antiviral and anticancer agents. Currently, he is working as a Research Fellow at the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. His research interests include anticancer drug design and synthesis, pharmacology and phytochemistry.
Abstract:
Lung cancer causes one third of death from cancer worldwide. In clinical, surgery, radiation therapy, chemotherapy, and targeted therapy are commonly used for the treatment of the malignancy. However, the success of these agents is limited due to the emerging of drug resistance. Th ereby, there is an urgent need to discover novel agents with improved efficacy and safety profiles for the treatment of lung cancers. We have recently synthesized a series of indolizino[6,7-b]indoles, which were designed as a hybrid molecule containing biologically active β-carboline (topoisomerase I and II inhibitory moiety) and bis (hydroxymethyl) pyrrole (DNA cross-linking moiety) for antitumor studies. Of these derivatives, we found that BO-1978 exhibited potent therapeutic efficacy against various non-small-cell lung carcinoma (NSCLC) cells both in vitro and in the tumor xenograft or orthotopic models. Remarkably, we found that the combination treatment of BO-1978 with gefitinib has enhanced efficacy against EGFR-mutated NSCLC and was superior to that of gefi tinib or cisplatin alone in tumor bearing mice. Moreover, this hybrid molecule displayed topoisomerases I and II inhibitory eff ects and induced DNA interstrand crosslinking. The studies on the toxicity/safety in mice revealed that this agent has low toxicity to the host; no major pathology or blood biochemistry changes. We also demonstrated that BO-1978 has good pharmacokinetic (PK) profile in animal. These findings indicated that BO-1978 can be selected as a candidate for preclinical study, IND application, and eventually for clinical trial for the treatment of NSCLC patient.
Hudson Caetano Polonini
Universityof Juiz de Fora, Brazil
Title: Improving bioavailabilty of Resveratrol: Transdermal, transmucosal and nanotechnology strategies
Time : 14:20 - -14:40
Biography:
Hudson Polonini, pharmacist, has completed his PhD at 2014 from Federal University of Juiz de Fora and currently performs postdoctoral studies from Federal University of Santa Catarina. He studies: analysis and control of medicines and related products, pharmaceutical and cosmeceutical technology, biopharmacy, natural products and ecotoxicology. He has published 30 papers in reputed journals and he has two patents, and he also has some awards in innovation competitions.
Abstract:
Resveratrol (3,5,4-trihydroxystilbene) is a prominent substance in currently pharmaceutical research. It is a naturally occurring non-flavanoid phenolic compound produced by some spermatophytes, notably grapes (reason why it is found in high concentrations in many red grape skins and their wines). The trans-resveratrol isomer is more biologically active: it has been reported to possess antioxidant, neuroprotective, antiphotoaging and antiviral activities, and it also seems to play a role in the prevention and reduction of pathological processes such as inflammation, cancer and heart diseases. However, trans-resveratrol has poor oral bioavailability, which creates a dilemma between its great in vitro efficacy and its low in vivo effect, mainly because it is extensively metabolized in the body. Our group has been dealing with this question. Two previous published studies on its permeations through excised human skin showed that this can be a good alternative to avoid the oral route. They used different methods and obtained very similar results of permeation percentage from emulsions (62.6 % using retention mapping and 64.9% using tape stripping). Another strategies that are currently under evaluation in our laboratory is the transmucosal route, either by oral or vaginal mucosal. Our preliminary results show that these seem to be also efficient routes, as they can act both for systemic drug delivery as for local clinical conditions. Finally, the inclusion of trans-resveratrol in solid lipid nanoparticles (SLN) is will offer additional advantages of stability and delivery of the substance to the body, as shown by the results obtained until now. In addition, toxicology studies are been run in parallel. These data altogether show that these alternative strategies can be safe and of clinical relevance for a more efficient delivery of resveratrol to humans.Thus, transdermal or transmucosal delivery of resveratrol is paramount for the effective insertion of the substance into pharmaceuticals for clinical practice.
Malihe-Sadat Poormasjedi-Meibod
University of British Columbia, Canada
Title: Composite Poly(methyl methacrylate)/Poly(ethylene glycol) electrospunnanofibrous mats as a novel wound dressing for controlled release of an anti-scarring agent
Time : 14:40 - 15:00
Biography:
Malihe is a second year PhD student in the Experimental Medicine Program under the supervision of Dr. Aziz Ghahary. She has joined the Burn & Wound Healing Laboratory in January 2011 after obtaining her Masters degree in Biotechnology form University of Tehran, Iran. Malihe’s project focuses on incorporating anti-fibrotic drugs into nanofibers in order to develop novel bioactive wound care products to treat dermal fibrosis. Malihe has expertise in protein purification and characterization, monoclonal and polyclonal antibody production and characterization, PCR, Western blotting and cell culture. In her free time, Malihe is volunteering as the president of Canadian Biomaterial Society student chapter. She also enjoys painting and outdoor activities.
Abstract:
Wound healing outcome is regulated by a fine balance between deposition and degradation of extracellular matrix (ECM). Over healing process in skin is mediated by exaggerated ECM deposition and abnormalities in ECM degradation. Moving toward novel approaches to prevent skin fibrosis, we identified a small molecule having anti-scarring properties which is called Fibrosis Stop 2 (FS2). Although daily application of FS2 containing cream eliminates evidence of scarring in a fibrotic rabbit ear model, an effective wound dressing, releasing controlled doses of FS2, will be more beneficial for FS2 delivery to extensive burns where the wound dressing get changed every 4-5 days. This study aims to develop novel biomedicated electrospun nanofibrouse mats for controlled delivery of FS2, directly to an injury site to improve the wound healing outcome. Nanofibers of Poly (methyl methacrylate) and different composite blends of Poly (methyl methacrylate)/Poly (ethylene glycol) with FS2, were successfully electrospun for the first time. Scanning electron microscopy was performed to determine the morphology and average diameter of the electrospunnanofibers. In vitro drug release evaluations showed that addition of PEG to PMMA has a proportional enhancing effect on the release of FS2 from nanofibrouse mats. While FS2-loaded PMMA/5% PEG mats showed significantly lower levels of burst release and prolonged release up to 5 days, medicated PMMA/20% PEG mats demonstrated complete drug release within 24 hours. The biological activity of the nanofiber incorporated FS2 was evaluated in vitro by determining the effect of these dressings on ECM components’ expression by fibroblasts. These studies showed that nanofiber incorporated FS2 significantly decreases the expression of collagen-I and α-smooth muscle actin and increases the expression of MMP1 which indicate the preservation of FS2 biological activity during the electrospinning process. Electrospinning of PMMA/PEG blend exhibited a useful and convenient method for controlling the rate and period of FS2 release in wound healing applications. The findings of this study confirmed that it is feasible to develop an anti-fibrogenic dressing for prevention of dermal fibrosis frequently seen upon burn, deep trauma and surgical procedures.
Alex Nivorozhkin
Neo-Advent Technologies LLC., USA
Title: Silica-based matrixes for drug delivery: Ready for a prime time?
Time : 15:00 - 15:20
Biography:
Nivorozhkin is an entrepreneur and a team builder in life sciences’ arena with vast experience and track record in an early technology transfer and development. He was a co-founding member of Boston BioCom, LLC, a biopharma company funded by the seed investment from Pfi zer. Alex gained substantial experience in the commercial aspects of drug discovery and development at Epix Medical and Inotek Pharmaceuticals where he served as the company’s Head of Medicinal Chemistry. He served as a Senior Program Manager at the Center of Integration of Medicine and Innovative Technologies (CIMIT) at Massachusetts General Hospital, a consortium of the Harvard Medical School-affliated hospitals, Boston University, Draper Laboratory and MIT aimed at developing new medical devices; and a Scientific Programs Officer at Sheldon and Miriam Adelson Medical Research Foundation. He is a co-inventor of several drug candidates that have advanced to clinical trials and late pre-clinical studies in the United States, has co-authored over 60 scientific publications in different areas of chemistry, chemical biology, and material sciences and holds more than 20 patents. Alex received a PhD in Physical Organic Chemistry from Rostov University and conducted the postdoctoral research at the University Paris-Sud, France, and the Department of Chemistry and Chemical Biology, Harvard University, Cambridge.
Abstract:
Sol-gel-derived and silica-containing materials have made significant strides into the material sciences’ applications and established presence in multiple commercial products and industrial technologies. In biomedical field, extensive researchindicated their potential utility in areas such as enzyme and live-cell encapsulation. These materials hold promise in a drug delivery area as well. General biocompatibility and biodegradable properties make silicas and sol-gels attractive matrixes. Nanotechnology brings in a possibility for a subtle tune-up of the particles fine structure and variety of functionalization opportunities for covalent and non-covalent binding of the cargo. This presentation will review key developments in using silica materials in drug delivery applications and focus on the properties and processes that could be controlling issues in moving early discovery findings into the realm of commercial applications and platform technologies that are compatible with FDA requirements for drug products to enter clinical trials.
Han-Chung Wu
Academia Sinica, Taiwan
Title: Development of ligand-mediated drug delivery systems for cancer targeted imaging and therapy
Time : 15:55 - 16:15
Biography:
Dr. Wu is currently a Professor and the Vice Director of the Institute of Cellular and Organismic Biology at Academia Sinica. He is also a Professor at the College of Medicine of the National Taiwan University. His research interest focuses on the development of targeting drug delivery systems for cancer therapy and targeting imaging. He has also developed phage display and affinity maturation methods to generate of fully human monoclonal antibodies for treatment of human diseases. Dr. Wu is actively involved in basic and translational research in the areas of oncology and has received numerous awards.
Abstract:
Lack of tumor specificity remains a major problem for chemotherapies in which side effects prevent the delivery of the drug dosages needed to eliminate the majority of cancer cells. Recently, we developed phage display methods to identify several novel peptides and human single chain variable fragment (scFv) antibodies that bind specifically to the plasma membrane of cancer cells. In an effort to develop targeting drug delivery systems, we used peptide-linked liposomes that carried doxorubicin to treat severe combined immunodeficiency (SCID) mice bearing human tumor xenografts. The peptide-functionalised liposomes were found to have an enhanced anti-tumor effect and reduced toxicity. Combination treatment of peptide-mediated targeting liposomes was able to completely eradicate tumors in three-sixth of the total number of tumor-bearing mice without any signs of recurrence. Targeting liposomes improved the therapeutic index by enhancing therapeutic efficacy, reducing side effects, and increasing the survival rate of tumor-bearing mice in orthotopic animal model. The tumor site fluorescent intensity in the mice treated with targeting peptide-linked quantum dots showed higher tumor uptake and increased tumor-normal tissue ratios. In addition, in vivo imaging by scFv-conjugated quantum dots clearly demonstrated the potential clinical use of the scFv in tumor targeting and imaging. Ligand-conjugated liposomes enhance pharmacokinetic and pharmacodynamic properties, improve efficacy and safety profiles, and allows for controlled biodistribution and drug release. Our study indicates that peptide- or scFv-mediated drug delivery systems show great promise for their applications in tumor-targeted drug delivery and imaging.
Khaled Mohamed Hosny
King Abdulaziz University, Saudi Arabia
Title: Enteric-coated alendronate sodium solid lipid nanoparticles; a novel formula to overcome barriers for the treatment of osteoporosis
Time : 16:15 - 16:35
Biography:
Khaled Hosny: Associate Professor of Pharmaceutics and Industrial Pharmacy at King Abdulaziz University, Saudi Arabia. He was granted his PhD from Cairo university, Egypt, in 2006. He is currently supervising 3 PhD & 8 Master degree postgraduate students. Dr. Hosny participated in the advanced research projects. Major research interests focused on Novel drug delivery systems. Dr. Hosny has a lot of publications in international journals.
Abstract:
Objective: The aim of this research was to utilize nanotechnology for oral alendronate sodium delivery, wherein ALS is incorporated within an enteric coated solid lipid nanoparticles (EC-SLNs). The putative advantages are enhancing the absorption and bioavailability, controlling the release, and preventing the free ALS from coming in direct contact with the GI mucosa thereby reducing the possibility of side effects.
Methods: (EC-SLNs) were prepared by a modified solvent emulsification-evaporation method based on a w/o/w double emulsion technique, effect of different process variables as solid lipid type, surfactant type and concentration, addition of charge inducing agent, enteric coating with Eudragit S100, and ultrasonication time on the particle size, zeta potential, entrapment efficiency, release in acidic and basic media were evaluated. Pharmacokinetic were conducted on rabbits
Results: EC-SLNs were successfully prepared with paricle size 74 nm, zeta potential 36 mV, and entrapment efficiency 56%. The nanoparticles released ALS only at pH 7.4 which ensure the efficiency of enteric coating. The bioavailability enhanced by more than 14 fold in rabbits.
Conclusion: EC-SLNs is a promising formula for the delivery of ALS, eliminating its oesophageal side effects, and enhancing its bioavailability.
Min Zhao
University College London School of Pharmacy, UK
Title: Exploring the critical stabilizing factors for solid dispersions without drug-polymer interaction: Monitoring and inhibiting amorphousamorphous phase separation
Time : 16:35 - 16:55
Biography:
Min Zhao completed her Ph.D from the School of Pharmacy, University of East Anglia, UK in 2010 and became a Lecturer in Pharmaceutics in the School afterwards. In 2013, Min joined the School of Pharmacy, University College London (UCL) and her main research focus has been on amorphous solid dispersion (ASD) technology as a means of improving the bioavailability of poorly water soluble drugs. Min’s talk on “Overcoming Devitrification of a Low Tg Drug by Spray Drying as a Solid Dispersion” has won the ‘Best Presentation Award’ at Amorphous III Conference run by the Academy of Pharmaceutical Sciences (APS).
Abstract:
Drug-polymer interaction and anti-plasticizing effect of the polymer are the two well-known mechanisms under which amorphous drugs may be generated and stabilized within solid dispersions. In this study, we deliberately select polymers which in the previous studies showed insignificant interactions with the drug of interest with a view to better understanding other factors determining the enhanced stability. Firstly, long term studies were performed under different stability conditions with a number of fully amorphous solid dispersions at varying polymer grades and drug loadings. The inhibition effect on morphologic change and water uptake appeared to be the key explanations for the stabilizing effects of polymers, varying with formulation and storage condition. In particular, PVP K29/32 was more effective for high temperature stability through sustaining the particle morphology while Plasdone S630 showed better stability over high humidity storage. Water uptake issue was further improved via incorporating zein (a class of prolamine protein) into the latter system. It was found that the binary system showed amorphous-amorphous phase separation while the ternary system remained stable through the entire testing period, indicating a significant inhibiting effect of zein on the water uptake of amorphous solid dispersions. Interestingly, the water induced amorphous-amorphous phase separation was well monitored using Transition Temperature Microscope (a novel method of nano-thermal analysis), which was supported by Differential Scanning Calorimetry and Scanning Electron Microscope techniques. In terms of the relationship between stability and dissolution performance, the occurrence of morphologic change and phase separation did not show profound effects on the drug release profiles.
Mine Orlu Gul
University College London School of Pharmacy, UK
Title: Coping with the management of medicine at old age: What older people think? What formulations scientists can do?
Time : 16:55 - 17:15
Biography:
Mine Orlu Gul is a pharmacist. She graduated from Istanbul University, Faculty of Pharmacy. She received her MSc on the subject of colon targeted microspheres in 2003, followed by a PhD about fl uorescently-labeled nanoparticles and their interaction with lung cells in 2008 from Istanbul University, Faculty of Pharmacy. During her PhD studies, she held a 1-year visiting scientist post at King`s College London funded by Marie Curie Host Fellowship for Early Stage Training in the 6th Framework Programme of the European Commission. She started The School of Pharmacy, University of London in March 2008 as a post-doc for Prof Oya Alpar to perform studies on vaccine formulations. In her second post-doc position, she joined Dr Catherine Tuleu`s group as a Teaching and Research Fellow at UCL School of Pharmacy, Department of Pharmaceutics, Centre for Paediatric Pharmacy Research to work in the fi eld of paediatric pharmaceutics and drug delivery. Her fellowship was funded by UK NIHR Medicines for Children Research Network (MCRN) from June 2009 to September 2012. She was appointed as Lecturer in Pharmaceutics to develop a research agenda in geriatric pharmaceutics in October 2012. She is a member of UCL Grand Challenges of Human Wellbeing Executive Group and Geriatric Medicines Society Age Appropriate Formulations Working Group. She also co-chairs The Academy of Pharmaceutical Sciences-Age Related Medicines Focus Group.
Abstract:
The current patient-centric formulation development specifi cally for geriatric patients is limited. However, steps are taken to improve the present status. Th e European Medicines Agency`s Geriatric Medicines Strategy, FDA`s Guidance of Industry E7 Studies in Support of Special Populations: Geriatrics - Questions and Answers document and EFPIA Position Paper on Drug Development for Older and Ageing Patients are promising to increase the availability of medicines tailored for needs of older patients. Th e review of current scientifi c literature shows that further research should be performed to rationalize formulation development for elderly. Besides the conventional biopharmaceutical properties of the drug and quality aspects of the formulation, organoleptic properties such as ease of swallowing, taste and simplicity of opening packaging should be considered at early stage of product development due the potential impact on patient acceptability. The presentation will cover several ongoing scientific studies to explore the pharmaceutical needs and solutions under the light of the opinion of older people obtained during public engagement workshops.
Rajiv Dahiya
Association of Pharmacy Professionals and Globus College of Pharmacy, India
Title: Bioactive peptides: Complex structures, synthesis and their controlled drug delivery
Time : 17:15 - 17:35
Biography:
Rajiv Dahiya is Doctor of Science in Clinical Pharmacology from International University for complementary Medicine, Colombo, Sri Lanka and Ph.D in Pharmacy from Uttar Pradesh Technical University, Lucknow, Uttar Pradesh), India. He is presently President of Association of Pharmacy Professionals (APP), editor-in-chief of international level journal - Bulletin of Pharmaceutical Research (BPR) and Principal at Globus College of Pharmacy, Bhopal, Madhya Pradesh, India. He has 13 years of teaching and 10 years of research experience. His research area is synthetic peptide chemistry and uptil now, he has published 50 research papers and 9 review articles in various international and national journals covering a total impact factor of 36.6. Dr. Dahiya is recipient of ‘Innovative Research Award’ in Jun 2012, ‘Excellence Award’ in Pharmacy in Feb 2014, ‘Young Pharmacist Award’ & ‘Young Scientist Award’ in Mar 2014.
Abstract:
Marine sponges and higher plants are enriched with several active constituents responsible for their biopotency. Among these, peptides have received special attention due to their wide biological profile including antimicrobial, anti-inflammatory, anti-AIDS, antimalarial, cytotoxicity, nematocidal, inhibitory activity against thrombin, trypsin, plasmin, tyrosinase and superoxide generation, calcium channel antagonistic activity and may prove better candidates to overcome the problem of resistance towards conventional drugs. Although linear peptides are associated with diverse bioactivities but cyclopolypeptides dominate over them due to the fact that inherent flexibility of linear peptides lead to different conformations which can bind to more than one receptor molecules, resulting in undesirable adverse effects. Furthermore, cyclization of peptides reduces the degree of freedom for each constituent within the ring and thus substantially leads to reduced flexibility, increased potency and selectivity of cyclic peptides. These cyclic congeners possess unusual or modified amino acid residues like Dhha, Adha, Ahoa, AHMP and exhibit their bioactivities through binding to corresponding enzymes. This characteristic feature can allow bioactive cyclopeptides to act as therapeutic agents in this resistant world. In order to design and develop long-acting, more effective peptide/protein drugs, the controlled release mechanisms and effective parameters need to be understood. Various peptide/protein delivery systems includes biodegradable and nondegradable microspheres, microcapsules, nanocapsules, injectable implants, diffusion-controlled hydrogels and other hydrophilic systems, microemulsions and multiple emulsions, and the use of iontophoresis or electroporation etc. Controlled delivery of peptide and protein drugs provides improved efficiency, reduced toxicity and improved patient convenience in addition to maximum stability, activity and bioavailability.
Saurabh Dahiya
Apeejay Stya University, India
Title: Guar gum revisited: Potential carrier for targeted drug delivery systems
Time : 17:35 - 17:55
Biography:
Abstract:
Guar also known as cluster bean is the source of a natural hydrocolloid which is cold water soluble and form thick solution at low concentrations. Owing to new technology, research and development being done in this field, the natural gum property has found varied applications from food to pharmaceutical industry. Due to its fascinating properties it is used as a rheological modifier. Guar gum can be modified by derivatization, grafting and network formation to alter its properties and make it suitable for biomedical applications. In order to enhance its applicability in the industries, its derivatization can be carried out to get novel derivatives with desired properties. Therapeutically it is used as hypoglycemic, hypolipidemic, antimicrobial, antiproliferative, appetite suppressant, bulk forming laxative in collitis and crohn's disease. The swelling property of guar gum is of importance in managing the drug release rate in innovative pharmaceuticals. The present talk is a review highlighting the total over-view from the plant to production to the application of this wonderful herb and its potential as a carrier for targeted drug delivery systems.
Sandeep Arora
Chitkara University, India
Title: Formulation and evaluation of neutraceutical tablets of lyophilized nanoparticles of Zinc and Asparagus extracts
Time : 15:20 - 15:40
Biography:
Sandeep Arora carries an impressive professional experience spanning 21 years—3.5 years in pharma production and quality assurance in Glaxo, Blue cross and 17.5 years in teaching/training and research—in the fi elds of pharmacognosy and natural products, regulatory affairs, industrial pharmacy, and management. He is the author of the book titled, “Pharmaceuticals – Issues for Industrial Management”; has been the honorary editor of “Advanced Drug Review”—a quarterly drug pharmacology review index—since 2005; and has to his credit about 50 national and international publications. His area of specialization and research are medicinal natural products (phytochemical, pharmacological evaluation and standardization), development and regulatory aspects of herbal and other products, and industrial management. Under his capable guidance two PhD students have completed their theses; 15 M. Pharm. students have completed their theses; and eight Ph D projects are currently being guided by him.
Abstract:
Herbal ZnO nanoparticles were synthesized using Asparagus root extract via co precipitation methods. Th e synthesized nanostructures were characterized by XRD, SEM and TEM which reveal the formation of crystalline ZnO nano-structures and spherical and granular nature with characteristic peaks of ZnO nanoparticles. Th e nanoparticles of Zinc and extract were also standardized for herbal marker component and Zinc and then tablet formulations were developed and standardized for formulation parameters. It was observed that the nanoparticles off ered a spherical and granular nature, which off ered very convenient advantage by producing very good preformulation characters including fl ow and particle size as compared to taking dry herbal powder as such which produce great diffi culty in tableting. Th e formulated tablets were standardized for formulation parameters on the basis of evaluation characteristics including disintegration time, dissolution time, friability and content for use as herbal nutraceuticals tablets and further development using various extracts.