International Conference and Expo on Biopharmaceutics September 21-22, 2015 Baltimore, MD, USA

Biography:

Alex 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, Neo-Advent Technologies LLC, Amorsa Therapeutics, an emerging company developing new medications and formulation approaches for treatment of the refractory pain, and other ventures. He 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 was as a Senior Program Manager at the Center of Integration of Medicine and Innovative Technologies (CIMIT) at Massachusetts General Hospital, 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. He 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. He is a Member of the American Chemical Society, Controlled Release Society, American Association of the Pharmaceutical Sciences and other professional organizations, active on the conference circle and serves as a co-chair of the Formulation and Drug Delivery Committee of the Massachusetts Biotechnology Council.

Abstract:

Abuse of opioids and other prescription controlled substances is a recognized nation-wide problem in United States and around the globe. Emerging FDA guidelines are setting up the ground rules for related evaluation and product labeling. As these documents point out, science of abuse deterrence is relatively new, and both the formulation technologies and the analytical, clinical, and statistical methods for evaluating those technologies are rapidly evolving. This presentation will focus on the overview of the existing and novel formulation approaches to enable tamper-resistant properties to include approaches involving physical/chemical barriers, agonist/antagonist combinations, aversion, delivery, and prodrug. Neither of the approaches can provide absolute protection and eliminate all the illicit options. So the question is, if there are clear pathways is assessing suitability of an appropriate technology for a given drug candidate or product and evaluating their readiness to be deployed. Up to date only a handful of tamper-resistant technological solution advanced far enough to be implemented into the market product. This number will certainly increase in near future as nascent and established tamper-resistant formulations will be further tested in clinical trials and interrogated by FDA.

Biography:

Amr Amin has completed his PhD at University of Illinois at Chicago, and received a post-doctoral training in the field of molecular genetics at the University of Pennsylvania School of Medicine. He started his academic career at UAE University where he serves now as a Full Professor of Cell Biology. Amr’s research focuses on ways to control cancer, particularly liver cancer. He published many research articles and reviews and serves as reviewer and as an editorial member of many specialized peer-reviewed journals. He is also a member of many specialized societies and the sole recipient of many scientific awards.

Abstract:

Hepatocellular carcinoma (HCC) is the second most common cause of cancerrelated death worldwide. The prognosis of patients with HCC is usually poor; hence, a novel approach against HCC is essential for a better therapeutic outcome. Saffron and its active constituents were reported to have antioxidant, anti-inflammatory, and anti-tumor properties. The aim of this study was to investigate chemopreventive action of crocin, one of the promising active constituents of saffron, against diethylnitrosamine (DEN)- induced liver cancer in rats, and the possible mechanisms by which crocin exerts its antitumor effects. Findings reported herein demonstrated the anti-proliferative and proapoptotic properties of crocin when administrated in DEN-treated rats. Additionally, crocin exhibited anti-inflammatory properties that inhibited NF-kB, among other inflammatory markers. According to our network analysis, NF-kB was identified as a regulatory hub, and therefore, a candidate therapeutic drug target. Together, these findings nominates crocin as a candidate chemopreventive and therapeutic agent against HCC.

Biography:

Dr. Monica C Chuong from Massachusetts College of Pharmacy & Health Sciences University, USA

Abstract:

Niacin and lovastatin are cholesterol lowering drugs. Niacin synthesized from tryptophan belongs to BCS class 1 with pKa 2.17 and plasma t1/2 20-48 min. Lovastatin naturally occurring in oyster mushrooms was isolated from Aspergillus terreus in 1982 and derived from red yeast rice in 1998. It is classified as BCS class 2 with pKa 13.49 andt1/2 4.5h. This presentation aims (1) to review lovastatin production using submerged culture vs. solid state fermentation of Aspergillus terreus and various chemically defined media, (2) toelucidate the fabrication ofa two-layer tablet design containing 250 mg niacin and 20 mg lovastatin, (3) to describe the formulation of a 20 mg lovastatin mini tablet in the delayed-then-extended dissolution release manner (without niacin). For aim 1, five literatures will be summarized. For aim 2, niacin heated with carnauba wax and stearic acid to blend. Once cooled, the solid mixture was tritulated with Carbomer 940 NF, Methocel K4M CR, sodium starch glucolate and Kollidone VA 64 to compress into a caplet. Ground mixture of lovastatin (the second drug), magnesium stearate, SDS and Avicel PH100 were added on top of niacin caplet to compress into the second layer. For aim 3, beta-cyclodextrin was complexed with lovastin (1:1 molar ratio) in hydroalcoholic solution. Once evaporated dried, this powder added with other excipients was compressed into mini tablets containing 20 mg lovastatin each. These cores were further enteric coated with a dispersion of Eudragit L 30D-55 and water (1:1 v/v). Content assay and in vitro release samples were quantified by HPLC.DSC confirmed no interaction between lovastatin and excipients. This project recommends that niacin (a rather acidic very water soluble small molecule) and lovastatin (an acid labile poorly water soluble macromolecule) be formulated separately.

Biography:

TBU

Abstract:

TBU

Biography:

Shobha Rani R Hiremath is a Professor and Principal of Al-Ameen College of Pharmacy, Bangalore. She is the recipient of Dr. Mumtaz Ahmed Khan Award for distinguished community service for the Exemplary and Yeoman Services rendered to the community through education in the year 2012. She is also the recipient of the 2006 STARS Award for Teachers for “Excellence in Academic Research” in recognition of merit in academic research and motivation to further the research of young minds. She has won 10best research paper awards. She has 80 research publications, 2 patents and 4 text books to her credit. Presently she is serving as Editor-in-Chief of the quarterly journal entitled Indian Journal of Pharmacy Practice (IJOPP) published by APTI. She has received research grants from AICTE, ICMR, WHO, AAGCPA and CDSCO (Govt. of India). Her research areas include Novel Drug Delivery Systems, Herbal Formulations, Clinical Pharmacokinetics and Pharmacovigilance. She has expertise in the formulation and evaluation of drug delivery systems such as Controlled delivery systems, Transdermal, Nanoparticles, Liposomes and Microspheres, Bioavailability-Bioequivalence studies and Pharmacokinetic studies and analysis.

Abstract:

Skin is a significant barrier for the penetration of hydrophilic drugs. Generally, chemical permeation enhancers have been utilized in the dermal and transdermal systems to enhance the delivery of drugs. However, use of chemical permeation enhancers is associated with several disadvantages. Particularly, enhancers such as glycols, terpenes, surfactants, solvents such as alcohol and DMSO have been found to cause dermal irritation and more severe side effects on prolonged use. Therefore, there is huge demand for safer and economical methods of drug permeation enhancement across the skin. The existing biophysical technologies such as iontophoresis, sonophoresis, microneedles, electroporation and laser ablation methods are known to perturb the skin barrier which would take considerable amount of time to recover. Some of the technologies are not patient compliant either. A technology that enhances the delivery of drugs across the skin without affecting the skin structure and barrier properties is required in the present scenario. Magnetically mediated enhancement of drugs is a novel and simple approach to enhance the transdermal delivery of drugs. The magnetic field could be generated by placing simple permanent magnets on the drug reservoir or as a backing membrane in magnetic field. In this presentation, the use of magnetic field in the transdermal patch system and its efficacy as compared to chemical enhancers will be discussed.The development of patch system in addition to the data of in vitro permeation test and pharmacokinetic studies in human subjects will be presented.

Biography:

Ghulam Rasool Mashori has completed his PhD at the age of 34 years from Faculty of Medicine, University Kebangsaan (National) Malaysia. He is the Director, Institute of Pharmaceutical Sciences and Peoples University of Medical & Health Sciences for Women Nawabshah (SBA), Sindh, Pakistan. He has published more than 20 papers in reputed journals. He has served with the Ministry of Health in various positions and also serving as an Editorial Board Member of repute Journals.

Abstract:

Treatment of hypertension has reduced the incidence of stroke, heart and renal failure. However the incidence of Coronary Heart Disease (CHD) is not reduced to the same degree. Many of the drugs advocated as first line drugs in step-wise therapy has been shown to cause carbohydrate intolerance, and it is an independent risk factor in the development of CHD. Since 1990’s individualized therapy in the treatment of hypertension has been advocated, whereby another class of antihypertensive drugs, such as calcium channel blockers (dihydropyridines) may be used as a first line therapy. Intracellular calcium plays important role in the excitation contraction coupling as well as the excitation-secretion coupling of hormones, including insulin. Absolute and relative lack of insulin can cause glucose intolerance. The purpose of the study was, to compare the effect of calcium channel blockers on insulin release from the rat isolated pancreas by perfusion technique, adapted from Loubatieries et al., 1972. The doses used were based on therapeutic peak plasma concentrations. Diazoxide has been used as positive control, i.e. known insulin suppressant drug. In the study Isradipine (10ng/ml) and Nicardipine (200ng/ml) showed significant suppression of the insulin release, this effect is dose dependent. Amlodipine (5ng/ml) significantly did not suppress the insulin release. Thus Amoldipine is found more useful drug amongst other calcium channel blocker. In conclusion different calcium channel blockers have varying effects on insulin release.

Biography:

Gulay Buyukkoroglu has completed her PhD from Anadolu University and Postdoctoral studies from University of London, The School of Pharmacy on transcutaneous DNA vaccination. She is Head of Pharmaceutical Biotechnology at Anadolu University Faculty of Pharmacy. She is working on gene delivery systems, new cancer drug delivery systems with siRNA and specific antibodies attached drug delivery systems and DNA vaccination.

Abstract:

The objective of this study is to prepare vaginal suppository containing chemotherapeutic agent and genetic material that can be applied locally in cervical cancer which is the second most frequently observed cancer type in women below the age of 45 and is generally resistant to chemotherapy. Paclitaxel has been selected as chemotherapeutic agent and siRNA that inhibits the BCL-2 oncogene has been selected as the genetic material. SLNs have been formulated in order to load the paclitaxel and siRNA to the vaginal suppository and to compare their effects. Paclitaxel loaded SLN, siRNA loaded SLN and paclitaxel/siRNA loaded SLNs have been dispersed separately in vaginal suppository prepared with PEG 6000. First, the physicochemical properties of SLNs, their cytotoxicities as well as the effects of siRNA loaded SLN on the protein amount expressed by the BCL-2 gene in the cells have been examined. Afterwards, the release of SLNs from the three different vaginal suppositories prepared has been determined via Horizontal Diffusion Chamber System. The paclitaxel amount loaded to the SLNs has been determined via HPLC whereas the siRNA amount has been determined via gel retardation system and UV spectrophotometer.

Biography:

Kaiser Jamil is Professor and Honorary Director for School of Biotechnology and Bioinformatics Mahatma Gandhi National Institute for Research and Social Action (MGNIRSA)

Abstract:

Acute Lymphoblastic Leukemia (ALL) is a hematopoietic cancer predominant in children and involves many aberrant pathways. There is a need to identify novel targets to improve our understanding of disease biology and for developing new therapeutics. Hence, the aim of our study was to uncover new genes as targets using in silico approaches. We first analyzed Oncomine micro array database to profile the top 10% overexpressed genes of significance. These were then prioritized using ENDEAVOUR, DIR and TOPPGene online tools to identify novel candidate disease genes. Thirty training genes, overexpressed in ALL were retrieved from PubMed literature search to train the tools. Further, the functional association networking of the prioritized and training genes was investigated using STRING protein interaction database. The network was then analysed using cytoHubba tool to identify highly connected hub genes. From our analysis of Oncomine database, 530 genes were shortlisted which on prioritization revealed fifty four genes to be significant candidate leukemogenic genes. Our hub analysis of the protein network led to identification of two novel genes, SMAD2 and CDK9, which were not implicated in leukemogenesis earlier. Filtering out from several hundred genes in the network we also found MEN1, HDAC1 and LCK genes to be important hubs, which re-emphasized their important role in leukemogenesis. This is the first report on these five additional signature genes in leukemogenesis. Our findings suggest that these genes could serve as new targets for developing novel therapeutics and also as biomarkers in leukemogenesis, which could be important for prognosis and diagnosis.

Biography:

M Shahnawaz Khan is currently a PhD student at Marine Biotechnology, National Sun Yat Sen University Kaohsiung, Taiwan. He did undergraduate in Honors Industrial Chemistry and masters in Industrial Chemistry from India’s prestigious university Aligarh M University, INDIA (2009). He is working on the hot topic like targeted drug delivery for curing cancer and employing photo-thermal method for releasing the drug at tumor region. He is concentrated on developing an effective method for wound control infection by using gold nanorods (Au NRs) and Nd-YAG laser (1064 nm) for photothermal killing Pseudomonas aeruginosa bacteria and simultaneously healing the wound infection on the (albino) mice. He is also curious to work on the brain diseases like Alzheimer, for it he synthesized the carbon nanodots and attached with Dopamine hydrochloride for efficient delivery to brain.

Abstract:

Graphene Oxide (GO), a close derivative of graphene has unlocked many pivotal steps in drug delivery due to their inherent biocompatibility, heavy drug loading capacity and high aqueous solubility. We used a novel plant material called Gum Arabic (GA) to increase the solubility of GO as well as to chemically reduce it in the solution. GA functionalized GO (fGO) exhibited increased absorption in Near Infra-Red Region (NIR) which was exploited in photothermal therapy for cancer. To augment the shape and size related problems of GO (which in turn affect their rheological properties), we have conjugated them with gold nano-rods (GNRs) using in situ synthesis of GO@GNRs via seed mediated method. To the above conjugate, Doxorubicin (DOX) was attached at ambient temperature (28±2 °C). Release kinetics of DOX with and without NIR exposure was also studied followed by in vitro photothermal killing of A549 cell lines. Enhanced NIR induced drug release as well photothermal property was observed which makes fGO@GNRs-DOX ideal for chemotherapy as well as photothermal therapy.

Biography:

Giulio Maria Pasinetti, MD, PhD, is the Saunders Family Chair and Professor of Neurology at the Icahn School of Medicine at Mount Sinai and Director of Basic and Biomedical Research and Training at the James J. Peters Veterans Affairs Medical Center. His research on co-morbidities influencing neurodegeneration has made him one of the top experts in his field. His principal focus is the prevention of neurodegenerative disorders even before the disease becomes symptomatic. He is the recipient of many awards, including the Faculty Council Award for Academic Excellence from the Mount Sinai School of Medicine, the Dana Alliance for Brain Research award, the Zenith award from the Alzheimer’s Association among others. Dr. Pasinetti is the recipient of over 30 grants and has published over 300 groundbreaking manuscripts.

Abstract:

Chromatin is the major regulator of gene expression and genome maintenance. Proteins that bind the nucleosome, the repetitive unit of chromatin, and the histone H4 tail are critical to establishing chromatin architecture and phenotypic outcomes. To modulate the chromatin structure, we designed a Nucleosome Binding Peptide – GMIP1- based on the crystal structure of RCC1 protein bound to a mononucleosome (PDB 3MVD). Molecular dynamic showed that GMIP1 tend to form an alpha helix, which suggests a more stable structure. For binding assays, we reconstituted mononucleosomes in vitro with 601 DNA -167pb- and histone octamer purified from chicken erythrocytes. The binding of fluorescent-labeled GMIP1 to a mononucleosome was observed by EMSA. To verify the GMIP1 effect in vivo, we performed MTT assays with different cell lines, such as Hela, Raw and skin fibroblast (CCD 1059). We observed a significant reduction of cells viability and proliferation with 50 uM of GMIP. In order to analyze the role of GMIP1 on the inflammatory pathway, we performed real-time PCR of TNF-alpha RNA extract from Raw cells. GMIP1 strongly reduced TNF-alpha expression and completely inhibited TNF-alpha stimulation by LPS, reducing fivefold the gene expression compared to non-treated cells. New experiments are on the way to check the peptide binding to nucleosome in cell based assays. Herein we present an exogenous Nucleosome binding molecule, a peptide, with intrinsic properties to modulate chromatin architecture and phenotypic outcome.

Biography:

Mircea Alexandru Mateescu is a PhD from Bucharest Polytechnic University and receiver of a “Honorary Laurea” from Rome University “La Sapienza”. He is a full Professor at UQAM since 1994. His research relates to Multifunctional Proteins and to Drug Targeting. He is the Co-inventor of more than 30 patents covering therapeutic enzymes and new excipients for drug delivery. He developed fruitful collaborations with pharmaceutical companies and was involved in several technological transfers. He published more than 130 papers in reputed journals, one book, and 8 book-chapters. He is the holder of Bombardier Prize (1999) for Technological Innovation, of Venezia Prize (Italian Chamber of Commerce, 2012), of Research-Career Prize (UQAM, 2014).

Abstract:

Biography:

Mircea Alexandru Mateescu has a PhD from Bucharest Polytechnic University and is a receiver of a “Honorary Laurea” from Rome University “La Sapienza”. He has been a full-time Professor at UQAM since 1994. His research relates to Multifunctional Proteins and to Drug Targeting. He is the Co-inventor of more than 30 patents covering therapeutic enzymes and new excipients for drug delivery. He has developed fruitful collaborations with pharmaceutical companies and was involved in several technological transfers. He published more than 130 papers in reputed journals, one book and 8 book-chapters. He is the holder of Bombardier Prize (1999) for Technological Innovation, of Venezia Prize (Italian Chamber of Commerce, 2012), and Research-Career Prize (UQAM, 2014).

Abstract:

Every year there are new therapeutic applications of proteins as carriers for bioactive agents of as active principles in treatment of various dysfunctions. Particular characteristics of proteins represent noteworthy cases of Molecular Self-Assembly in nature. Proteins drastically change their structure following various processing events such as heating, pH modification or action of ionic agents. These structural alterations can be useful for the utilisation of proteins as carriers (micro- and nano-spheres) for various bioactive agents or as biomedical materials (suture for surgery, skin grafts). However, these drastic alterations can be damaging for orally administered proteins susceptible to gastric acidity and proteolytic denaturation. New approaches in protein formulation are needed related to specific requirements for these biomolecules which can lose their activity due to processing temperature or to residual humidity remaining after coating. The proposed concepts are related to compacted pharmaceutical compositions containing one or more therapeutic enzymes designed for oral administration. The biopharmaceutical product could be under monolithic or multiparticulate forms and obtained without the application of an external polymer-based enteric coating. The self-assembled uncoated proteins are able to generate in situ an outer layer which will offer a gastro-protection and keep product availability. An example of excipient-free pancreatic enzyme will be discussed. The colonic delivery of an anti-inflammatory enzyme system based on a vegetal histaminase and on catalase will be also presented.

Biography:

Pompilia Ispas-Szabo is Adjunct Professor at Université du Québec à Montreal (UQAM, Canada) and a Research & Development scientist in pharmaceutical industry. She completed her M.Sc in Physical Chemistry at Bucharest University and the Ph.D. at UQAM. Co-inventor of new excipients proposed as matrices for controlled drug delivery or new products, she worked in various Canadian pharmaceutical companies (Smartrix Technologies, IntelGenx Corp., Aptalis Pharma, etc.), being involved in the development of innovative products or technological platforms. Co-author of 10 patents/applications, more than 30 papers in reputed journals, one book, two book-chapters, member of Controlled Release Society and AAPS, and reviewer for several international journals, she is recognized for her contribution to academic and industrial innovation.

Abstract:

Macromolecular self-assembly represents an interesting way to produce materials for various therapeutic applications (targeted drug delivery, bioactive encapsulation). Considerable interest relates to the design of polymer- or peptide-based self-assembled biomaterials due to the possibility to generate different specific properties by new arrangements at molecular level. Differently from existing approaches which explore mainly the drug-excipient association in order to improve solubility, we are proposing a new alternative – the drug-drug self-assembling, using two different active molecules. Mesalamine (5-aminosalicylic acid, MES) is an efficacious active ingredient used for the long-term therapy of inflammatory bowel disease. However, its oral administration is frequently associated with systemic side effects caused by drug absorption in the upper gastrointestinal tract. Sucralfate (SUC) is a non-systemic site protector prescribed in the treatment of inflammation and gastric ulceration. The anti-inflammatory action of MES in association with bioadhesiveness and mucosal healing properties of SUC were considered promising for the development of a new compound containing both molecules, aimed as an improved treatment of ulcerative colitis. The present case investigated the capacity of the two active agents to interact and generate a new and stable entity via self-assembling. Spray-drying was used to co-process the two active principles from an aqueous mixture. Preliminary in vitro studies with oral solid dosage forms based on the obtained MES-SUC complexes have shown a controlled MES release, opening the perspective of a new colon-targeted delivery system and a novel class of compounds with therapeutic application in inflammatory bowel diseases.

Biography:

Margarida Barroso is an Associate Professor at the Center for Cardiovascular Sciences, Albany Medical College in Albany, NY. She received her PhD, in Genetics from the University of Lisbon/Gulbenkian Institute of Sciences in Portugal and was a Post-doctoral fellow at the Department of Molecular Biology, Princeton University. She is in a faculty instructor in several international imaging courses and has two issued patents on FRET imaging technology. She belongs to the following scientific societies: American Society of Cell Biology (ASCB), Biophysical Society, Histochemical Society, and Sigma Xi. Since 2008, she is a member of the governing Council of the Histochemical Society. She has published more than 25 papers in reputed journals and acts as a reviewer for several internationally recognized journals.

Abstract:

Traditional cancer therapy generally leads to harmful side effects, thus warranting development of targeted therapies, which are better tolerated by cancer patients. Our goal is to develop in vivo non-invasive optical imaging assays for optimization of anti-cancer drug targeted therapy. We have established a fluorescence lifetime Förster Resonance Energy Transfer (FL-FRET) non-invasive whole-body in vivo tomographic imaging technique that can discriminate bound and internalized near-infrared (NIR)-labeled transferrin (Tfn) from free, soluble NIR-Tfn. This FRET-based assay exploits the homodimeric nature of transferrin receptor (TFR) that binds two molecules of Tfn in close proximity to determine dimerization and internalization of TFR-Tfn complexes into cancer cells. The Tfn FRET assay has been validated in vitro by visible and NIRFRET microscopy. FL-FRET tomographic imaging in vivo has been used to measure the internalization of tail-vein injected NIR-Tfn into human breast T47D tumor xenografts in live nude mice. Quantification of FRET donor % (FD%) in T47D tumor xenografts in vivo, indicates a higher proportion of FD% with increasing acceptor:donor ratio, demonstrating tumor uptake of NIR-Tfn. Tfn uptake concentration curve shows high sensitivity of FL-FRET imaging using NIR-Tfn as low as 10µg/ml of blood. Furthermore, relative high FD% for holo-Tfn (iron-loaded) compared to that of apo-Tfn (iron-depleted) demonstrates specific TFR-mediated uptake of holo-Tfn by T47D tumor xenografts, as expected since iron-depleted apo-Tfn shows reduced binding affinity towards TFR. In conclusion, we have successfully demonstrated the quantitative receptor-mediated uptake of Tfn into human breast tumors in vivo using a novel non-invasive NIR FL-FRET tomographic imaging assay.

Biography:

Taosheng Chen completed his Ph.D. from the University of Vermont, and postdoctoral studies from the University of Virginia. He is an Associate Member (Associate Professor) and Director of the High Throughput Screening Center at St. Jude Children’s Research Hospital. Prior to joining St Jude, Taosheng was a Senior Research Investigator at Bristol-Myers Squibb, and a Research Scientist at SAIC-Frederick, National Cancer Institute. Taosheng serves on the Editorial Boards of several journals, and on NIH Grant Review Panels. He has authored more than 80 publications. His research laboratory studies the roles of nuclear receptors in therapeutic efficacy and toxic effects (http://www.stjuderesearch.org/chen/).

Abstract:

Xenobiotic receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) regulate drug toxicity and resistance, which are the leading causes of treatment failure and for which no clinically safe and effective remedy is available. PXR and CAR play central roles in activating the expression of CYP3A4, a major enzyme responsible for metabolizing more than 50% of clinically prescribed drugs, and ALAS1, a rate-limiting porphyrin biosynthesis enzyme that increases the levels of hepatotoxic protoporphyrin IX (PPIX), both contributing to drug-induced liver toxicity. Elevated MDR1 level is associated with drug resistance. MDR1 expression is induced by CAR and PXR. While PXR is ligand-inducible, CAR is constitutively active. Therefore, inhibitors of PXR and CAR (i.e., antagonists of PXR and inverse agonists of CAR) may prevent drug-induced liver toxicity and overcome drug resistance. By using a chemical biology approach we have identified and optimized PXR antagonists and CAR inverse agonists, investigated their mechanisms of action by performing structural and functional analysis, and evaluated their in vivo activities by using humanized animal models. Our data indicate that it is feasible to prevent drug-induced liver toxicity and overcome drug resistance by targeting PXR and CAR using mechanism-guided chemical agents.

Biography:

Margarida Barroso is an Associate Professor at the Center for Cardiovascular Sciences, Albany Medical College in Albany, NY. She received her PhD, in Genetics from the University of Lisbon/Gulbenkian Institute of Sciences in Portugal and was a Post-doctoral fellow at the Department of Molecular Biology, Princeton University. She is in a faculty instructor in several international imaging courses and has two issued patents on FRET imaging technology. She belongs to the following scientific societies: American Society of Cell Biology (ASCB), Biophysical Society, Histochemical Society, and Sigma Xi. Since 2008, she is a member of the governing Council of the Histochemical Society. She has published more than 25 papers in reputed journals and acts as a reviewer for several internationally recognized journals.

Abstract:

Traditional cancer therapy generally leads to harmful side effects, thus warranting development of targeted therapies, which are better tolerated by cancer patients. Our goal is to develop in vivo non-invasive optical imaging assays for optimization of anti-cancer drug targeted therapy. We have established a fluorescence lifetime Förster Resonance Energy Transfer (FL-FRET) non-invasive whole-body in vivo tomographic imaging technique that can discriminate bound and internalized near-infrared (NIR)-labeled transferrin (Tfn) from free, soluble NIR-Tfn. This FRET-based assay exploits the homodimeric nature of transferrin receptor (TFR) that binds two molecules of Tfn in close proximity to determine dimerization and internalization of TFR-Tfn complexes into cancer cells. The Tfn FRET assay has been validated in vitro by visible and NIRFRET microscopy. FL-FRET tomographic imaging in vivo has been used to measure the internalization of tail-vein injected NIR-Tfn into human breast T47D tumor xenografts in live nude mice. Quantification of FRET donor % (FD%) in T47D tumor xenografts in vivo, indicates a higher proportion of FD% with increasing acceptor:donor ratio, demonstrating tumor uptake of NIR-Tfn. Tfn uptake concentration curve shows high sensitivity of FL-FRET imaging using NIR-Tfn as low as 10µg/ml of blood. Furthermore, relative high FD% for holo-Tfn (iron-loaded) compared to that of apo-Tfn (iron-depleted) demonstrates specific TFR-mediated uptake of holo-Tfn by T47D tumor xenografts, as expected since iron-depleted apo-Tfn shows reduced binding affinity towards TFR. In conclusion, we have successfully demonstrated the quantitative receptor-mediated uptake of Tfn into human breast tumors in vivo using a novel non-invasive NIR FL-FRET tomographic imaging assay.

Biography:

Keerat Kaur is currently a PhD student in Department of physiology at New York Medical College, NY. she have completed her undergraduate and master degree in the field Human Genetics from Guru Nanak Dev University, Amritsar, India. Presently, she is working on the project entitled ‘Examining pharmacological approaches for enhancing the cardiac regenerative capacity of adult stem cells’. In the ongoing project, she is trying to characterize the benefits of pharmacological treatments for enhancing the potential of adult tissue- derived stem cells to form myocardial tissue. As, stem cell therapy has been widely accepted for its ability to give rise to differentiated cells, we are constantly developing new culture conditions that would allow to enhance the number of stem cells and also differentiate them into mature cardiac tissue. In the second project, she is examining the capability of human bone marrow cells to produce functional cardiomyocytes which can later become a source of fully differentiated cells for transplantation. The long term goal of her study is to focus on procedures that would allow the adult stem cells as a real target for clinical management.

Abstract:

Stem cell therapy has been widely used in attempts to repair and regenerate the diseased heart. Since the heart does contain endogenous cardiac progenitor cells (CPCs), heart tissue itself has served as a stem cell source for cardiac repair. Impediments in using CPCs for treating human patients are that the cells are present in low numbers within the heart and require heart biopsies, which may not be efficacious for severely diseased individuals. Two major objectives in optimizing the therapeutic utility of CPCs are to enhance their cardiac regenerative capacity and expand their numbers without sacrificing their cardiac competency. Our laboratory has focused on utilizing pharmacological approaches for promoting the myocardial potential of adult stem cells. Two of the drugs we have investigated are the DNA demethylation reagent 5-azacytidine and the G9a histone methyltransferase inhibitor BIX01294.

Biography:

Dr. Meghana Vidiyala from Ascent Pharmaceuticals, USA

Abstract:

The objective of this work is to develop and characterize Nano-emulsion based transdermal system (NTS) having Lidocaine in Nano-emulsion form. This second generation Nano-emulsion based transdermal drug delivery system has several advantages over traditional gel and transdermal systems (TS). NTS are therapeutically more effective compared to gel and conventional transdermal patches. Nano-emulsion components including surfactants and co-surfactants enhance skin permeability thereby increasing therapeutic efficacy and bioavailability of the drug molecule. Moreover, the release profile can be modulated by altering the ratio between surfactant, co-surfactant, and solvents.

Biography:

Anamaria Orza focuses primarily on the area of development of innovative architectural nano camposites for biomedical applications. Prior to her arrival at Emory in the fall of 2013, Dr. Orza served as a postdoctoral researcher at the Center for Integrative Nanotechnology Sciences at the University of Arkansas at Little Rock. Dr.Orza has been recognized as a European Union fellow, receiving her PhD in Chemistry from Babes Bolyai University, Romania and working in close collaboration with Liverpool University, United Kingdom. Dr. Orza has authored and co-authored 2 patents and over 32 papers in leading journals and at leading international conferences in the field (with over 170 citations) and 2 book chapters in the fields of Applied Nanotechnology in Cancer Research and Tissue Engineering. anamari

Abstract:

In this study, we report on the synthesis and characterization of shaped iron oxide core palladium shell (Fe2O3-Pd) as three-modality image agents in Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Photo-Acoustic (PAT) imaging. Four shapes were synthesized such as: triangular plates, tetrapods, pyramidal structures and pentagon shaped nanoparticles. We report for the first time their synthesis using an original approach by uniformly fusing multiple components and by controlling their structural (i.e., size, shell thickness, dimer shape) and physical characteristics (i.e., optical, and acoustic). To confer enhanced properties for efficient targeted capability, the surface of the nanoparticles was modified with (i) the amphiphilic di-block polymer and (ii) functionalized with the ligands targeting transferrin receptor (Tr). As a result, the newly created shaped nanoparticles were characterized via different optical and imaging techniques (HR-TEM, STEM, XPS, EDX, Z-potential, and UV-VIS). We show that the shaped Fe2O3-Pd nanoparticles are stable and biocompatible in given Fe concentrations range and display shaped control MRI/CT/PAT attenuation intensity. The attenuation intensity subsequently decreases as follows: tetrapods>pyramidal>pentagons>triangular plates. Moreover, these shaped nanoparticles enable targeting imaging of tumor cells that have a high expression of the transferrin receptor. These findings conclude that the designed Fe2O3-Pd are promising contrast agents for targeted MRI/CT/PAT molecular imaging.

Biography:

Deborah Quintanilha Falcão has completed her PhD at the age of 32 years from cooperation between Universidade Federal do Rio de Janeiro (Brazil) and Université Montpellier I (France) and postdoctoral studies from Oswaldo Cruz Foundation (Brazil). Actually she is professor of Pharmaceutical Technology at Faculty of Pharmacy from Universidade Federal Fluminense (Brazil). She has published more than 15 papers in reputed journals, 5 book chapters and serving as an editorial board member of repute.

Abstract:

Spices have been used since ancient times for a large number of purposes, such as medicinal, perfume, preservative and to confer aroma and flavour to food. They still play an important role in the traditional medicine as part of pharmaceutical preparations and several monographs are reported in the official pharmacopoeias. Extracts obtained from medicinal plants are generally complex mixtures of organic substances produced as plants secondary metabolites. Increased cases of opportunistic diseases emanating from side effects associated with synthetic drugs continue to necessitate incremental efforts in searching for effective biological substitutes with little or no side effects. Therefore, many studies have been performed with medicinal plants in order to overcome this problem, intending the discovery of new molecules of therapeutic interest. In this regard, the application of nanotechnology tends to make this more feasible due to the ideal small size of the particles, releasing the substance in the correct location and time. The choice of wall material and production method is therefore of paramount importance and combined with the ability to modify drug release, makes such nanosystems ideal candidates for therapeutical purposes presenting a wide range of applications. The nanotechnology combined to the natural products chemistry can bring an important contribution to the development of new delivery systems, promising candidates as new products with important perspective on health improvement. The aim of this work is to offer an overview on nanoencapsulation of natural products covering development challenges and future perspectives.

Biography:

Gozde Unsoy has received her PhD in Biotechnology from Middle East Technical University (METU), Turkey under Dr. Ufuk Gunduz in 2013. Her PhD thesis focused on the discovery of novel targeted drug delivery systems has been chosen for the “Best Thesis of the Year Award” at METU. She is currently studying on the in vitro and in vivo efficacy anti-cancer drug loaded nano carriers developed by her as a Post-Doctoral Research Scientist. She has published more than 18 papers in reputed journals and is serving as an Editorial Board Member of repute.

Abstract:

Chitosan coated magnetic iron-oxide nanoparticles (CSMNPs) can be targeted to the tumor site under magnetic field and maintain pH dependent drug release. Among various materials, chitosan has a great importance as a pH sensitive, natural, biodegradable, biocompatible and bio-adhesive polymer. CSMNPs were in-situ synthesized at different sizes by ionic crosslinking method. XRD and XPS analyses proved that synthesized iron-oxide was magnetite (Fe3O4). Chitosan coating on magnetite was detected by FTIR and chitosan amount was 23% in TGA. CSMNPs were found super-paramagnetic by VSM. Average core size was 8 nm in TEM and hydrodynamic diameter was 103 nm in DLS. The anti-cancer drug doxorubicin was loaded on CSMNPs (Dox-CSMNPs) and loading was confirmed by FTIR. 30% of doxorubicin was released at pH 4.2 in first 7 hours. Dox-CSMNPs are efficiently taken up by MCF-7 and 1 µM Doxorubicin resistant MCF-7 (MCF-7/Dox) breast cancer cells. CSMNPs increase the efficacy of Doxorubicin by increasing the cellular uptake of drug and overcome the resistance of Doxorubicin in resistant cells. When these drugs are loaded on CSMNPs, the anti-proliferative efficiencies of drugs increases and resistance to these drugs is eliminated. In vitro cytotoxicity analyses also revealed that IC50 values of drug 13 fold decreases when loaded on CSMNPs. Pro-apoptotic Puma and Noxa genes were up-regulated while anti-apoptotic Bcl-2, Survivin and cIAP-2 genes were down-regulated in Dox-CSMNP treated cells. This study provides new insights to the development of pH responsive magnetic targeted drug delivery systems to overcome the side effects and resistance problem of conventional chemotherapy.

Biography:

Dr. Papadopoulos is a graduate of the School of Pharmacy of the University of Athens. He completed his PhD in Health and Life Science at Université Pierre et Marie Curie, Paris and post-doctoral studies in France and Australia. In 1988, he joined the faculty of Georgetown University School of Medicine, where he rose through the ranks to become Professor and Chair of the Department of Biochemistry and Molecular Biology, Associate Vice President for research and then Director of the Biomedical Graduate Research Organization. In 2007, he moved to Montreal as the Executive director and chief scientific officer of the Research Institute of the McGill University Health Centre. He is Professor in the Faculty of Medicine at McGill University and holds a Canada Research Chair in Biochemical Pharmacology and the Phil Gold Chair in Medicine. Dr. Papadopoulos has published over 300 papers, holds numerous patents and serves on national and international advisory committees. He is an elected foreign member of the National Academies of Medicine and Pharmacy in France, fellow of the American Association for the Advancement of Science, and fellow of the Canadian Academy of Health Sciences.

Abstract:

Biotechnological medicines have improved the treatment of various diseases and the quality of life of patients. The administration of a drug may lead to adverse events that may or may not be documented. These events affect disease progression and health expenditures. Rheumatoid Arthritis (R.A.) is an autoimmune disease for which biotechnological medicines are prescribed. RA has serious economic impact. Especially, the annual cost of RA is 41 billion Euros in the U.S.A. and 45billion Euros in Europe, which are increasing dramatically with appearance of an adverse event.

Biography:

Will be Updated Soon

Abstract:

Graphene oxide (GO), a close derivative of graphene has unlocked many pivotal steps in drug delivery due to their inherent biocompatibility, heavy drug loading capacity and high aqueous solubility. We used a novel plant material called Gum arabic (GA) to increase the solubility of GO as well as to chemically reduce it in the solution. GA functionalized GO (fGO) exhibited increased absorption in near infra-red region (NIR) which was exploited in photothermal therapy for cancer. To augment the shape and size related problems of GO (which in turn affect their rheological properties), we have conjugated them with gold nanorods (GNRs) using in situ synthesis of GO@GNRs via seed mediated method. To the above conjugate, Doxorubicin (DOX) was attached at ambient temperature (28±2°C). Release kinetics of DOX with and without NIR exposure was also studied followed by in vitro photothermal killing of A549 cell lines. Enhanced NIR induced drug release as well photothermal property was observed which makes fGO@GNRs-DOX ideal for chemotherapy as well as photothermal therapy.