Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 8th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems Madrid, Spain.

Day 3 :

Keynote Forum

Amiram Goldblum

The Hebrew University of Jerusalem, Israel

Keynote: Current Problems in Drug Discovery and some in silico Solutions

Time : 09:30-09:55

Conference Series Pharmaceutica 2016 International Conference Keynote Speaker Amiram Goldblum photo
Biography:

Amiram Goldblum is the Head of the Molecular Modeling at the Hebrew University of Jerusalem. He has completed his PhD in Organic Reaction Mechanisms, Jerusalem and Postdoctoral studies of Quantum Biochemistry in Paris and QSAR and QM reaction mechanisms in California. He has developed semi-empiricalrnMNDO/H for dealing with H-bonding in large molecular systems and moved to algorithmic development for dealing with extremely complex problems, for which hernreceived an Award of the COMP division of ACS in 2000.

Abstract:

Main concepts in drug discovery and design will be examined using protein structures from X-rays for docking and discovering drugs, the single disease single target concept as well as associated issues of selectivity and side effects. Targeting two or more proteins in order to produce single multi-targeted molecules may prove to be a better avenue to effective drugs. Many disease conditions like cancers, bacterial and viral infections, hypertension, neurological disorders and diabetes are currently treated by "drug cocktails" or by single targeted drugs. Those and others have more than a single biochemical pathway or several targets in a pathway leading to disease, therefore multi-targeted single drugs could be more effective than current treatments. Attempts to block proteins to prevent harmful enzyme reactions or protein-protein interactions are failing due to the involvement of these proteins in reactions with other substrates or partners. Therefore the concept of "substraternselective inhibition" (SSI), the tailoring of an inhibitor to block a single or a few and to avoid other substrates has been developed earlier but may be advanced by using computations. I will present an algorithm called "Iterative Stochastic Elimination" that can supply ideas for novel and diverse molecules that are predicted and proven to have multi-targeting abilities and will suggest approaches to the SSI problem.

  • Track 3: Recent Advances in Drug Delivery Technology
    Track 7: Major Challenges in Drug Delivery System
    Track 11: Medical Devices for Drug Delivery
Location: Melia Avenida America
Speaker

Chair

Amiram Goldblum

The Hebrew University of Jerusalem, Israel

Speaker

Co-Chair

B B Barik

Jazan University, KSA

Session Introduction

Paul Fisher

Inovio Pharmaceuticals Inc, USA

Title: Enhanced delivery of DNA-based vaccines and immunotherapeutics through next-generation electroporation devices

Time : 09:55-10:15

Speaker
Biography:

Paul Fisher is a Bioengineering Scientist at Inovio Pharmaceuticals, where he is investigating the delivery of DNA-based therapeutics. He received his B.S. in Biomedical Engineering from the University of California, Irvine, and his Ph.D. in Biomedical Engineering from the University of Kentucky. Dr. Fisher has a background in controlled drug release from implantable and injectable biomaterials, with a focus on regenerative medicine. He has two patents pending for his work on novel sustained drug delivery systems using biodegradable polymers.

Abstract:

It is well known that naked DNA vaccination alone is insufficient to generate clinically relevant immune responses due to inefficient cellular uptake. In vivo electroporation (EP) has been shown as an efficient non-viral method for enhancing DNA vaccine delivery and immunogenicity in animals and humans over the past twenty years. In a recent randomized, double-blind, placebo-controlled phase 2b study, Inovio Pharmaceuticals has successfully demonstrated therapeutic vaccination of CIN2/3 patients with VGX-3100, a highly optimized HPV-16/18 DNA vaccine, administered by CELLECTRA® EP device resulted in robust cellular and humoral immune responses, significant viral clearance and, importantly, significant regression to CIN1 or no disease. Inovio is currently developing additional EP devices for DNA delivery to a variety of tissues, such as muscle and skin. One of the examples- Surface Electroporation Device (SEP), which only contacts the surface of the skin and does not penetrate the skin, is capable of efficient delivery of DNA vaccines into the skin while establishing that these parameters are sufficient to elicit both robust and sustainable humoral as well as cellular immune responses without tissue damage. Here we will discuss the impact of these devices on in vivo DNA uptake and how different EP strategies can be used to optimize delivery of DNA-based vaccines and immunotherapeutics for a variety of therapeutic indications for different applications.

Speaker
Biography:

Dr. Catarina Duarte has a PhD in Physical-Chemistry (1997, Universidade Nova de Lisboa). She is the head of the Nutraceuticals and Delivery Group of IBET,Portugal (since2003), coordinator of R&D activities and responsible for technology transfer between academia and industry. Research interests include the development of clean technologies for the development of new functional formulations, with application in pharmaceutical, cosmetic or food industries. Regularly provides support for innovation, research and development of new products. She is author of 88 accepted papers in peer-reviewed scientific periodicals, several book chapters and communications in international meetings.

Abstract:

Intranasal route have emerged in last years as an effective approach, even to brain delivery of drugs, as the brain and nose compartments are connected to each other via the olfactory/trigeminal systems. With this purposes, biocompatible drug delivery systems (DDS) including polymer-based or lipid-based systems have been studied and many formulations developed. In the present, new DDS such as multilayered microspheres and hybrid [polymer-lipid] dry forms are considered as alternative. This presentation will focus on the application of high pressure processes (e.g. supercritical fluid technology) as an alternative to conventional precipitation processes, and a precipitation technique that avoids completely the use of organic solvents will be presented. As exemples, the results on two hybrid delivery systems: [Gelucire 43/01™:PEG 4000] and [Gelucire 43/01™:GMO], produced by the PGSS® method(Particles from Gas Saturated Solutions) will be shown. Moreover, alginate-based hybrid aerogels (with low methoxyl pectin and κ-carrageenan), in the form of microparticles dried with supercritical CO2, will be presented as carriers for mucosal administration of drugs. These DDS were designed to allow the improved absorption of low molecular weight drugs or peptides after their administration though nasal mucosal tissue.

Gavin Walker

University of Limerick, Ireland

Title: Bioactive PCL matrices with a range of structural & rheological properties

Time : 11:05-11:25

Speaker
Biography:

Since 2012, Professor Gavin Walker has been awarded >€20,000,000 as Principal Investigator, specifically contributing to advanced in Chemical Engineering on 15 projects from EU (H2020, FP7, Marie-Curie), UK government (TSB, EPSRC) Irish Government (SFI, EI), UK Charities and Industrial sources. Prof. Walker is PI on Pharmaceutical Manufacturing Technology Centre (PMTC); PI on EI Dairy Processing Technology Centre (DPTC); Synthesis and Solid State Pharmaceutical Centre (SSPC) at the University of Limerick.

Abstract:

Safer pharmaceutical and medical devices excipient are being sought as alternatives to polyvinyl polymers that are commonly plasticised by carcinogenic phthalates. This paper demonstrates a biodegradable and non-toxic bioactive polymer matrix whose structural and rheological properties can be easily modified by the amount of added plasticiser, while being only mildly affected by the presence of a low dosage API. Poly(ε–caprolactone) (PCL) was selected as an alternative polymer to polyvinyls as it is biodegradable and has high amorphous content, which improves drug solubility. Bulk PCL and various blends with 5 and 25% polyethylene glycol (PEG, a plasticiser and pore former) and 5% nalidixic acid (NA, the bioactive) were processed using extrusion and pressed into plaques. The resultant material properties were investigated in terms of microscopic, morphological and topographical modification. No evidence of miscibility was found by IR. The rheology and contact angle of the matrix could be easily manipulated through the addition of PEG. An increased loading of PEG to 25% (w/w) caused a 10 fold increase in the melt flow index, a similar increase in the elongational viscosity, and a contact angle decrease of 10°, indicating that the resultant fluid was becoming more Newtonian. It was concluded that the structural and rheological properties of the blend, while easily modified through the addition of PEG, were unaffected by the monodispersion of the API, nalidixic acid.

Break: Networking & Refreshments Break - 11:25-11:40

Luisa Fiandra

University of Milan, Italy

Title: Targeted inorganic nanodevices for breast cancer diagnosis and therapy

Time : 10:35-10:55

Speaker
Biography:

Luisa Fiandra has completed his PhD and postdoctoral studies from the Department of Biology of the University of Milan (Unimi), working in the field of transport physiology with a specific interest in permeability processes through intact epithelia and cell membranes. From 2010 to 2015 LF has been senior researcher at L. Sacco Hospital (Milan), where she contributed establish the Nanomedicine Unit, and scientific coordinator of the NanoMeDia Project, funded by Regione Lombardia (Italy). Today, LF is carrying out her research activity, mainly focused on the breast cancer targeting and therapy by nanoformulated drugs, and on the delivery of antiretrovirals across biological barriers, at the Department of Biomedical and Clinical Sciences “L. Sacco” of Unimi.

Abstract:

Among the various kinds of tumors, breast cancer represents a target of primary interest, both from a diagnostic and a therapeutic point of view. In this context, powerful target-specific magnetic nanodevices can represent efficient contrast agent for MRI detection and good delivery system for anticancer drugs. Nowadays, many efforts are devoted to design nanosystems which can be localized at cancer cells for an extended period of time, in order to optimize diagnostic sensitivity and therapeutic efficiency. A valid example is represented by a versatile molecular superparamagnetic nanocomplex, functionalized with the commercial anti-human epidermal growth factor receptor 2 (HER2) trastuzumab (TZ) or TZ-derivatives. Several in vitro and in vivo experiments demonstrated the dependence of HER2 targeting efficiency from the structural features of the immobilized homing ligands. Moreover, the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting and therapeutic effect was demonstrated. The best in vivo activity was obtained with monofunctionalized Tz- as compared with bifunctionalized Tz-nanoparticles.

Break: Networking & Refreshments Break 10:55-11:10 @ Salamanca

Havazelet Bianco-Peled

Technion–Israel Institute of Technology, Israel

Title: Composite hydrogels: An innovative approach for controlled release of hydrophobic drugs

Time : 11:10-11:30

Speaker
Biography:

Havazelet Bianco-Peled is a Professor of Chemical of Engineering since 1999. She has received several awards for her professional accomplishments. She has written more than 70 research publications in reputed journals, edited a book, and has ten patent applications either granted or pending. She is the Founder and CSO of SEAlantis Ltd., a company that develops, manufactures and commercialize novel biomimetic tissue adhesives base on a technology invented in her lab.

Abstract:

Many of the new medical entities are extremely hydrophobic. These drugs offer advantages such as better targeting and efficiency. However, their low water solubility is related with low bioavailability and risk of aggregation upon intravenous administration. We present an innovative methodology for sustained delivery of hydrophobic drugs using composite hydrogels, prepared by embedding oil-in-water microemulsions in hydrophilic hydrogels. Creating composite hydrogels increases drug loading due to its higher solubility in the oil droplets, while the crosslinked hydrogel matrix could be readily used as a solid controlled delivery vehicle. We formulated alginate and chitosan composite hydrogels from pharmaceutical accepted components. The oil droplets diameter was shown to be 10 nm by dynamic light scattering, cryo-TEM and SAXS. All hydrogels were capable of loading hydrophobic compounds with a wide range of logP. The gels were clear with no precipitations, indicating the solubility of the drugs in the gels. Release profiles from hydrogels with various concentrations of polymer and crosslinker demonstrate the applicability of this system as a controlled delivery vehicle, and suggest that the release rate is governed by the network properties. The release from alginate composite hydrogels was similar for different microemulsion formulations, various drugs and increasing concentrations of a drug. These findings indicate that these hydrogels could potentially act as a generic system, where the properties of the release do not depend on the drug but rather on the attributes of the gel. The release mechanism from chitosan hydrogels was more complex due to polymer–microemulasion interactions.

Speaker
Biography:

Dr. Abdelazim Zaghloul is an Associate Professor of Pharmaceutics at Faculty of Pharmacy, Kuwait University. He earned his BSC of Pharmacy fromAlexandria University and his MSc and PhD Degrees in Pharmaceutics from Al-Azhar University, Egypt. From1999-2003, he worked as a Postdoctoral Research Fellow at School of Pharmacy, Texas Tech University. Dr. Zaghloul has published more than 30 articles in per-reviewed international journals and presented more than 50 podium and poster presentations to national and international meetings. Dr. Zaghloul main research interest focus on drug delivery, design and development of various dosage forms, physicochemical characterization and evaluation of critical process and formulation variables by optimization procedures and neural networks.

Abstract:

Metformin hydrochloride (MtHcl) is an oral antidiabetic drug and has been used successfully to treat polycystic ovary and overweight patients. However, the available commercial dosage form is the oral tablets that has poor bioavailability, narrow absorption window and extensive first pass metabolizm in the liver. The aim of this work was to formulate MtHcl as a rectal suppository dosage form to partially bypass the liver metabolism, improve the absorption and bioavailability and to be a good alternative for children and elders who cannot take the oral tablets. For this purpose , suppository fatty bases (Witepsol®, Suppocire® and Massa®; different grades) and PEG bases 1000, 4000 and 6000 (different ratios), were used to prepare rectal suppositories each containing 500 mg drug by fusion method. The formulations were characterized for mechanical strength, melting time, penetration time, content uniformity, and in-vitro drug release. Based on the results, three formulations containing Witepsol H12 (F1), Suppocire AP (F2) and Massa Estranium B (F3) were chosen for bioavailability testing in human volunteers using the commercial oral tablets (500mg) as a reference (Ref). The results indicated that the preparation method applied produced suppositories with satisfactory characteristics. The fatty bases were superior compared with PEG bases. The average melting time for F1-F3 was 8 min, the drug content uniformity ranged between 95-105%, the mechanical strength ranged between 7-8kg/cm, the penetration time ranged between 6-8 min and the in-vitro drug release was more than 90% in the first hour of dissolution time. The in-vivo results were: Tmax 0.25, 0.5, 0.25, 3 hr; C max 7254.11, 8319.19, 8423.36, 1125.01 ug/ml for F1, F2, F3 and Ref, respectively The % relative bioavailability for F1, F2, F3 against the Ref. were 76.65, 100.95 and 99.01 respectively. In conclusion, the results indicated that MtHcl rectal suppositories were successfully prepared and characterized and the fatty bases showed better characteristics compared with the PEG bases. F2 and F3 showed comparable bioavailability with the commercial tablets. MtHcl formulated in fatty bases could be a potential alternative to the commercial tablets particularly for pediatric and geriatric patients.

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Title: Speaker Slot Available

Time : 12:40-13:00

Biography:

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Break: Lunch Break - 13:00-13:40
Speaker
Biography:

Dimitris Hatziavramidis has completed his BSc at NTUA (Greece), his MSc at University of Manchester (UK) and his PhD at University of Illinois (USA). He has spent most part of his career working for academic institutions and large corporations in the USA and is currently a professor at NTUA. Prior to this, he served as a professor and Director of the Particle Technology and Crystallization Center for pharmaceutical products, in the Department of Biological and Chemical Engineering at Illinois Institute of Technology in Chicago, IL. He is a Fellow of AIChE. He has published extensively in reputed journals and has several patents.

Abstract:

Age-related macular degeneration (AMD) is a progressive, neurodegenerative, occular disease and a leading cause of irreversible loss of vision in aging adults in developed countries. Its pathogenesis is characterized by uncontrolled proliferation of cells and cell growth in blood vessels, leaking of blood and proteins and aberrant folding, aggregation and accumulation of proteins. Overexpression of the vascular epithelial growth factor (VEGF) causes uncontrolled blood vessel growth resulting in violation of the blood-retina barrier and accumulation of blood and protein debris causes neurodegeneration of cells in the retinal pigmented epithelium (RPE) and tissue disfunction. The current treatment of AMD is primarily based on anti-VEGF drugs which are administered by intravitreal injection. It has been recently proposed to administer exogenous Heat shock proteins such as Hsp70 by intravitreal injection in order to clear accumulated debris from RPE and inhibit aggregate-based cell neurodegeneration. An equally effective and less vision-threatening than intravitreal injection route of administration of the above macromolecular drugs is transscleral delivery from an implant in the posterior eye, thermally-sensitive A study for sustained delivery of an anti-VEGF agent to the posterior eye from an implant, made of a poly(N-isopropylacrylamide) (NIPAM) thermally sensitive gel. This gel undergoes a phase transition characterized by a lower critical solution temperature (LCST) of 33oC, below which the drug is loaded in the gel and above which the drug is released from the gel.

Speaker
Biography:

Amiram Goldblum is the Head of the Molecular Modeling and Drug Design and Discovery Unit at the Institute for Drug Research of the Hebrew University. Following a BSc in Chemistry and Physics and a MSc in QM studies of molecular spectra, his PhD is in Organic Reaction Mechanisms (Mechoulam, Hebrew U). He completed his Post-doctoral studies of Quantum Biochemistry (Paris), QSAR and QM reaction mechanisms (California). He receieved his first award at the American Chemical Society National Meeting in Washington DC 2000 for his algorithm called "Iterative Stochastic Elimination" (ISE) used to solve extremely complex combinatorial problems and focuses in recent years on Molecular Discovery by Chemoinformatics.

Abstract:

Liposomes are the most extensively clinically used drug delivery system. Since the FDA approval of the first nano-drug Doxil®, more than 12 other liposomal drugs were approved by the FDA and more liposomal drugs are under development. Doxil is based on the combination of high and stable drug loading which is also responsible for the controlled drug release as well as on the use of nano-pegylated liposomes. Pegylated nano-liposomes are important for treating cancers, neurodegenerative and inflammatory disorders, as they take advantage of the enhanced permeability and retention (EPR) effect and deliver drugs to the site of disease. Development of liposomal formulations is a time consuming process which requires major efforts. A more rational and less labor intense process is, taking advantage of computational modeling approaches capable of predicting whether an active pharmaceutical ingredient (API) could be loaded to and delivered by liposomes. Towards that end, Quantitative Structure– Property Relationship (QSPR) models were developed with iterative stochastic elimination and k-nearest neighbors approaches to predict drug loading efficiency (high vs. low) in liposomes. Chemical as well as formulation descriptors were employed and the resulting statistically validated models were used to screen a few thousand biologically active molecules from the Comprehensive Medicinal Chemistry database. Three drugs were selected for experimental testing of their loading into nano-liposomes, also taking into account challenges of nano-liposomal development. Two of the selected drugs were high-and one was low-loading, confirming the predictions. Ten other negative molecules from literature were also confirmed, to a total prediction accuracy of 92%. Screening results of CMC database were obtained by the two computational approaches (ISE and kNN). One of the tested drugs- mupirocin, was remotely loaded into pegylated nano-liposomes, and stabilized by intraliposomal hydroxypropyl-β-cyclodextrin to form nano-mupirocin, which was evaluated in vivo for its therapeutic efficacy. Mupirocin, an antibiotic with a unique mode of action is currently restricted to topical administration due to its rapid degradation in the blood. Intravenous administration of nano-mupiricin to mice in necrotizing fasciitis model showed significant superiority of nano-mupirocin over mupirocin. Our approach demonstrates the utility of QSPR models in screening API libraries for identifying candidates that should benefit from being administered as nano-drugs.

Speaker
Biography:

Prashant Shalikram Khemariya is a well known young scientist of India. His expertises are in the field of Pharmaceutical and Biotech Products Development. Now days he is based in Malaysia and working with one of the leading Pharmaceutical Company in Research and development. He has more than 15 international and National research/ review publications and few are under process. For last 6 years he has been on the journey of research. He has successfully developed more than 80 ANDA products and worked with NDA Molecules. In wound and cancer Management Prashant Shalikram Khemariya is very enthusiastic.

Abstract:

According to WHO- International and domestic funding for malaria control and elimination was approx US$ 2.7 billion in 2013, even after that 3.2 billion people, almost half of the world’s population are at risk of malaria. Not only were that till September 2015, there 214 million cases of malaria and 438,000 deaths. As per American Mosquito Control Association (AMCA) there are approx 3000 varieties of mosquitoes and Culex, Anopheles, and Aedes genera are the most common and most dangerous responsible to Malaria and Dengue fever. 120000 mosquitoes would be enough to completely drain out the blood of average human just within 3 minutes of short time. So no wonder to say that mosquitoes have been described as the “world’s deadliest animal”. Mosquito likes dark colors (most favorite black) and O+ blood is very delicious for them, resulting people with O+ blood group are always on mosquito’s demands. Actually, only the female mosquitoes bite people, but not for her meal, although they are searching Isoleucine in human blood that is one of the basic building blocks of life. Human blood is not the best source for Isoleucine, blood from buffaloes and rats contains more Isoleucine, but since people outnumber rats and buffaloes in many places the mosquitoes bite us instead. Female mosquito may lay as 200-300 eggs if she has Isoleucine otherwise only 10. Female Anopheles Gambiae is one of the best known for a predominant role in the transmission of the most dangerous malaria parasite species called Plasmodium falciparum. Female mosquitoes have nerve cells called cpA neurons that have a receptor to detect carbon dioxide and chemicals secreted through human skin. An average person’s respirations generate approximately 450 liters of carbon dioxide, 1500 mmols of lactate and expel few chemicals from the skin per day, by thee smell of these chemicals mosquitoes tracks our location. The aim of presenting research is to make a hollow statue containing few thin layers of soft gelatin (tensile strength 15-20 MPa) and that will be reacting as a Human body. The outer layer will be dark black with 1.5-2.5 mm of thickness and have “Chemical A” ( containing L-Lactic Acid, ammonia, carboxylic acids, Carbon Dioxide and octenol in a particular combination) and an inner layer will be approx 2-3 micron of thickness, 12-20% of moisture and overlap with a W/O emulsion of a Carbamate. Outer layer of the statue will release “Chemical A” (containing CO2 and other chemicals) in mist form, this chemical will be enough to attract female mosquitoes. To drill outer layer of the statue a female mosquito will need 15-17 Hz, pressure and a vibratory cutting frequency of 200-400 Hz by her fascicle with 1.8mm length and 11.0 mm internal radius, now condition will be same as epidermis (outer layer of human skin). When mosquito will sit on outer layer and drill it, fascicle reaches to an inner layer of statue that having Carbamate in liquid form and she will suck it. Carbamate actually affect the activity of acetylcholinestearase (AChE), which is responsible for the hydrolysis of acetylcholine (ACh), it is a neurotransmitter. This chemical act as synapses in the Central Nervous System of the mosquito. Following the inhibition of AChE caused by carbamylation, ACh will accumulate thus prolonging the action of the Neurotransmitter at the cholinergic synapses, resulting hyper excitation of the CNS will accompanied by convulsion, then paralysis and ultimately it will lead to the death of the mosquito. One State will be enough for 2.80 Sq acres are and few more statues will make entire city free from Mosquitoes.

  • Track 8: Physiological Considerations
    Track 9: Vaccine Drug Delivery Systems
    Track 10: Biotherapeutics-Drug Discovery and Development
Location: Melia Avenida America
Speaker

Chair

Osama Ibrahim

Bio Innovation, USA

Speaker

Co-Chair

Helen McCarthy

Queen’s University Belfast, UK

Speaker
Biography:

Osama O Ibrahim is a highly-experienced Principle Research Scientist with particular expertise in the fields of biochemistry, microbiology, molecular biology, and bioprocessing for both pharmaceutical and food ingredients. He was External Research Liaison for Kraft Foods with Universities for research projects related to bioprocessing and molecular biology. In the 2005, he accepted an early retirement offer from Kraft Foods and formed his own biotechnology company (Bio Innovation) providing technical and marketing consultation for new start-up biotechnology and food companies. He holds three bioprocessing patents and received his PhD in basic medical science (Microbiology, Immunology and Molecular biology) from New York Medical College. He is a Member of American Chemical Society, American Society of Microbiology, and Society of Industrial Microbiology since 1979.

Abstract:

Angiogenesis is a highly controlled process of growing new blood vessels under normal circumstances. However, in a large number of pathologies, such as solid tumor growth, angiogenesis is a crucial component of the disease process. Therefore, inhibitors of angiogenesis are being investigated as potential therapeutics for tumor growth. During angiogenesis endothelial cells of existing blood vessels undergo a complex process of reshaping, migration, growth, and organizing into new vessels. Vascular Endothelial Growth Factor (VEGF) is a central mediator of this process and acts via receptors whose expression is restricted almost exclusively to endothelial cells. Because of its selectivity, VEGF represents a unique vehicle for delivery of inhibitors of angiogenesis to endothelial cells. Among potential inhibitors of angiogenesis, the shiga-like toxin-1 (SLT-I) produced by E. coli O157:H7 has the advantage that endothelial cells appear to be particularly sensitive to its action. The hypothesis that combining an SLT-I toxin with VEGF as a delivery vehicle would serve as a highly selective and active inhibitor of angiogenesis. To this end, fusion proteins containing VEGF121 and two forms of shiga-like toxin-I (SLT-I) were developed and tested in vitro for activities that have the potential to inhibit angiogenesis in vivo. Plasmids encoding the fusion proteins VEGF121/A1 containing the catalytically active fragment of the SLT-I A subunit and VEGF121/A containing the full length A subunit of SLT-I were constructed in pET-29a and pET-32a systems. Escherichia coli BL21 (DE3) pLysS bacteria were transformed with the plasmid constructs for the expression of these two fusion proteins. Both purified fusion proteins inhibited the translation of luciferase mRNA as a reporter gene in vitro translation system, indicating that both fusion proteins retain the N-glycosidase activity of SLT-I. However, only VEGF121/A1 fusion proteins displayed the ability to induce auto-phosphorylation of the VEGF receptor KDR/FLK-1 and displayed a strong, selective growth inhibition of cultured cells expressing KDR/FLK-1 receptors. These results indicated that VEGF/SLT fusion proteins are promising therapeutic agents that can be developed into powerful and selective inhibitors of angiogenesis.

Helen McCarthy

Queen’s University Belfast, Northern Ireland

Title: A new technology for DNA vaccination: RALA peptide-mediated gene delivery via dissolving microneedles

Time : 12:10-12:30

Speaker
Biography:

Dr Helen McCarthy obtained her PhD in 2000 from University of Ulster. She then took a Research Associate post in the field of prostate cancer gene therapy at the University of Ulster. In July 2004 she moved to the School of Pharmacy, Queen's University Belfast to take the post of Research Fellow on a cancer gene therapy project, within the newly established, Experimental Therapeutics research cluster. She obtained a lectureship within the School of Pharmacy in November 2006, then Senior Lecturer in 2011 and Reader in 2013. For the last 10 years Dr McCarthy’s research team have focused on the development of non-viral delivery systems for nanomedicine. These biomimetic systems are designed to overcome the extra and intracellular barriers, so that the macromolecular payload can be delivered at the destination site in order to exert the optimal therapeutic effect. Dr McCarthy has published widely (>50 research papers), holds several patents on delivery systems in the nanotechnology area and has given numerous invited conference presentations. She has obtained significant research grant income from MRC, BBSRC, EPSRC, Cancer Research UK, Prostate Cancer UK, Breast Cancer Campaign, Royal Pharmaceutical Society of Great Britain, The Royal Society, National Science Foundation, Invest NI and Touchlight Genetics. She has also collaborated extensively both nationally and internationally and sits on the editorial board for Cancer Nanotechnology.

Abstract:

Cervical cancer has the second highest mortality rate amongst women worldwide, despite the production of recombinant protein HPV vaccines. Limited access in poorer regions, the prophylactic nature of current vaccines and poor patient compliance contribute to a rising incidence. Furthermore, the current vaccine is not effective for those patients with pre-existing HPV lesions. DNA vaccination evokes both therapeutic and prophylactic responses. The bottleneck in the DNA vaccination market lies in an effective delivery technology. The ‘solution’ to this problem is in the two-pronged approach of our technology: (i) a peptide delivery system, termed RALA, that is able to wrap the DNA into nanoparticles, protect the DNA from degradation, enter cells, disrupt endosomes and deliver the DNA to the nucleus and (ii) a microneedle patch (MN) that will house the nanoparticles within the polymer matrix, painlessly breach the skin’s stratum corneum barrier and dissolve upon contact with skin interstitial fluid thus releasing the nanoparticles into the skin to the antigen presenting cells. Using our novel technology platform we have created a DNA vaccine for cervical cancer in a dissolvable microneedle patch. More specifically the MN patch is loaded with RALA/E6-E7 nanoparticles and this study demonstrates stability, functionality and a prophylactic and therapeutic response to cervical cancer tumours in vivo. The RALA/E6/E7 nanoparticles were characterized in terms of gel retardation, size and zeta-potential analysis and transmission electron microscopic imaging. The functionality of the RALA/E6-E7 nanoparticles within the polymeric microneedle matrix was assessed by analysis of transfection efficacy in fibroblast NCTC cells via western blot analysis. Cellular toxicity was also assessed via WST-1 assay. C57/BL6 mice were immunized with the RALA-E6/E7 in a prime-boost-boost regimen and blood serum was isolated to measure specific IgG responses and IFN-γ levels via ELISAs. C57/BL6 mice were also immunised with the MN-RALA/E6-E7 patches and challenged with cervical cancer. A therapeutic response study was performed in vivo. Finally the RALA/E6-E7 nanoparticles were lyophilised to increase the dose that can be loaded into the MN patch. Results proved that RALA was essential for stability of the E6-E7 DNA in PVP and that MN-RALA/E6-E7 evokes a more consistent humoral mediated immune response. Tumour challenge studies indicate the MN-RALA/E6-E7 vaccine patch is preventing the uptake of tumours and treating established tumours. Doses greater than 50 μg were achieved from a single MN patch. We have, therefore, created a fully functional prototype MN/RALA/E6-E7 DNA vaccine for cervical cancer.

José Crecente Campo

Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Spain

Title: Nanotechnology and mucosal vaccines

Time : 12:30-12:50

Speaker
Biography:

Dr. José Crecente is a researcher at the University of Santiago de Compostela (USC). He holds several degrees in Industrial Engineering, Science Food and Chemistry apart from a master degree in Drug Discovery and Development and a PhD in Organic Chemistry. He has also worked as a visiting scientist at Cambridge University in the group of Prof. Steven Ley. Over the last 3 years Dr. Crecente has been associated to the laboratory of Prof. Alonso, at the USC, where he has been involved in the formulation of proteins and antigens. Currently, he is involved in 4 vaccine-related projects, among them a NIH project and a EU (NANOPILOT) project, both oriented to the preclinical development and scaling-up of nanovaccines.

Abstract:

Vaccination has been, without any doubt, the greatest success of medicine in preventing diseases. Infections that centuries or even decades ago caused decimation of whole cities and countries nowadays are old ghosts of the past or have much less impact in human beings. In the constant effort of science to increase quality of life, vaccines based on living or attenuated microorganisms that provoked severe side effects have evolved to vaccines based on safer antigens, like purified proteins, peptides and plasmids. However, these last compounds are much less immunogenic and for that reason the use of adjuvants is becoming imperative in the development of modern vaccines. Among these adjuvants, nanoparticulated systems have emerged as ideal candidates thanks to the advantages they can offer like (i) to protect the integrity of the antigen, (ii) to improve and prolong the antigen presentation to the immune system cells and (iii) to modulate the immune response towards the cellular or humoral arm. Besides, nanosystems can be an ideal platform to administer vaccines through the mucosal routes with some important benefits like (i) better mucosal response, (ii) needle-free vaccination, (iii) better compliance of the patient, and (iv) easier production. Nanotechnology is providing us more and more sophisticated platforms like nanoparticles, ISCOMs, nanocapsules, bilosomes, etc. and probably, in the near future we will see a mucosal nanovaccine in the market.

Speaker
Biography:

John received a BS in biochemistry from Albright College and his Ph.D. in synthetic organic chemistry from Brown University. After completing a Postdoctoral Fellowship at the Sloan-Kettering Cancer Institute in NYC in the departments of Positron Emission Tomography and Neurology, he joined the Medicinal Chemistry Discovery group at Johnson Matthey Biomedical. There he worked on Pt-based antitumor drugs and diagnostic radio-imaging agents. He later moved on to drug development, in positions of increasing responsibility at J&J and Sanofi Aventis. For the past 15 years he and his teams have specialized in the areas of drug delivery and solid state chemistry, focused at the interface of drug discovery and development. His specific expertise in drug delivery lies in the area of enhancing the solubility of insoluble compounds, where he has successfully introduced a wide range of methods into drug discovery space. More recently, he has been active in the design of prodrugs for improving physicochemical properties or targeting for specific disease states. He currently is a Senior Principal Scientist and Global Technology Lead in the Discovery Pharmaceutical Sciences department at Merck Research Labs. Spanning his 25 year career, he is co-inventor on 13 US Patents and author of numerous publications and book chapters in the fields of organic, solid state & medicinal chemistry and drug delivery.

Abstract:

ver the past decade, scientific and business needs have pushed Pharma to more closely align drug discovery and drug development efforts in order to bring optimal preclinical drug candidates (PCCs) forward. Towards this end, Pharma development chemists at Merck now routinely provide innovative rationally designed drug formulations ranging from nanoparticles to amorphous dispersions for key preclinical animal studies. They also work closely with medicinal chemists to optimize PCCs’ physicochemical properties and identify a crystalline phase that has appropriate characteristics that will allow for good performance in pre-clinical safety studies and clinical formulations. In all cases, miniaturization and state-of-the art characterization methods are essential. Early investment in these areas can significantly shorten the time to the clinic and help avoid ugly surprises related to API phase and exposure. One of the most exciting aspects of working in this space is the many opportunities for innovative collaboration between biologists, chemists, pharmacologists, etc., investigating new drug delivery modalities and administration routes in a wide range of preclinical species. This presentation describes the unique tools a Merck uses in discovery space and shows some examples where partner groups from Discovery and Development worked together to increase the speed of drug lead identification, biopharmaceutical optimization and the PCC clinical approval process.

Biography:

I completed the PhD from University of Bradford and I am a chemist who has taught Chemistry in the Department of Chemistry, College of Science, King Saud University for more than 5 years. I interested in research and follow recent discoveries in science, particularly Chemistry, by reading the literature.

Abstract:

A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. In particular, some compounds displayed antibacterial activity against two methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentrations (MICs) comparable to the widely-used drug ciprofloxacin. The compounds have some common features; three possess 5-halo substituents; two are derivatives of (S)-2-ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl)-1H-benzo[d]imidazole and (1H-benzo[d]imidazol-2-yl)methanethiol. The results from the antifungal screening were also very interesting: 23 compounds exhibited potent fungicidal activity against the selected fungal strains. They displayed equivalent or greater potency in their MIC values than amphotericin B. The 5-halobenzimidazole derivatives could be considered promising broad-spectrum antimicrobial candidates that deserve further study for potential therapeutic applications.

Break: Lunch Break 13:10-13:55 @ Salamanca
Speaker
Biography:

Afaf BENHOUDA has completed his PhD at the age of 27 years from Algeria University and she did her PHD at University of Degli Salerno –Italy and the dempartment of Farmacia Fedderico II Italy. She published 4 articles ans she has 15 internationan and national congres in Cybrus, Antalya, Edirna, Istanbul, Marrakech, Pekin.

Abstract:

The present study is to evaluate the protective effect of methanolic extract of the leaves of the plant Umbilicus rupestris against hepatotoxicity induced by the ethanol and also to evaluate th inflammation induced by the carrageenan. In heptoprotective activity, five groups of 4 rats were treated respectively with distilled water, absolute ethanol ,URMeOH (100 mg / Kg b.w.), URMeOH (200 mg / Kg b.w.) and quercetin used as the reference standard, these treatments were administered orally 30 minutes before the administration of absolute ethanol for 14 days. The results showed that administration of EtOH increased significativeley the level of biochemical parameters TGO, TGP, ALP and BTof pathologic control but the effect of the extract shows that the oral adminstration of (100 and 200 mg / Kg) and quercetin caused a significant decrease (p≤0.05) of these parameters. For anti-inflammatory activity, Wistar rats were divided into four groups of four rats. The extract was administered orally with doses (100 and 200 mg/ kg b.w) and indomethacin (50 mg / kg) then the Carrageenan (2%) was injected intraperitoneally1 hour later.The protective effect of the extract was evaluated by measuring the number of leukocytes recruited into the peritoneal cavity.The pretreatment with the extract(100 and 200mg /kg b.w.) decreased significantly the number of leukocytes (P≤0.05) compared to the control group.

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Title: Speaker Slot Available

Time : 15:40-16:00

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Break: Networking & Refreshments Break - 16:00-16:15
Speaker
Biography:

Abstract:

The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was studied. By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar. At neutral pH, binding of TT conjugates to AlPO4 was facilitated through the carrier protein, with only weak binding of AlPO4 to CRM197 being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM197–conjugates. This was verified in AlPO4 formulations containing DTwPeHib, where the adsorption of TT-conjugated Hib was higher than CRM197–conjugated Hib. At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions. Phosphate ions reduced the binding of the conjugates to the adjuvants. These patterns of adjuvant adsorption can form the basis for future formulation studies with individual and combination vaccines containing saccharide-protein conjugates.

Speaker
Biography:

Muhammad Akhtar has completed his PhD in the year 2014 from The Islamia University of Bahawalpur, Pakistan. He is currently working as an Assistant Professor of Pharmaceutics at Department of Pharmacy, The Islamia University of Bahawalpur. He has published more than 20 research and review articles in reputed national and international journals and has been serving as reviewer for research journals of good repute. He has university teaching experience of more than 10 years to teach the students of PharmD and MPhil (Pharmacy). He has presented his research at national and international conferences.

Abstract:

The study was aimed to evaluate pharmacokinetic parameters of sustained release combined formulation of ibuprofen and misoprostol tableted microspheres. The study was conducted in 18 healthy male volunteers. A single dose as tablet was administered through oral route. The plasma concentrations of drugs were assessed by development of reverse phase HPLC method and blood samples were taken over a period of 12 h post drug administration. Non-compartmental method of analysis was used for evaluation of pharmacokinetic parameters. Maximum plasma drug concentration (Cmax) and time (tmax) to reach Cmax were determined directly from the data. Area under plasma concentration time curve from time zero to time of last quantifiable concentration (AUC0-t) was calculated using linear trapezoidal rule. In addition, absorption parameters were also calculated. Kinetica® software version 4.4.1 was used for these calculations. Computer based MS-Excel was used to determine mean ± SD values. The current HPLC method was found suitable for simultaneous determination of ibuprofen and misoprostol. The Cmax values (mean ± SD) of 26.68±2.32 and 0.17±0.01 for ibuprofen and misoprostol were observed, respectively. The values (mean ± SD) of T¬max and AUC0-∞ were 1.89±0.47 and 179.81±22.87 for ibuprofen while 1.36±0.54 and 0.84±0.04 for misoprostol, respectively. The current study reported improved bioavailability and estimation of the quantifiable concentrations of both drugs in plasma for a prolonged period of time by successfully developing a fixed-dose combination of both IBN and MIS as tableted microspheres.

Speaker
Biography:

Tejeswararao D has completed his PhD from Indian Institute of Chemical Technology, Hyderabad. He is working as Assistant Professor in GMRIT, Rajam. He has published 2 papers in reputed journals and presented in 8 proceedings. He is the Chairman of REES Society (non-profit organisation).

Abstract:

A diversity-oriented synthesis has been developed for facile construction of a library of quinoxaline derivatives. The synthetic protocol is suitable for generating quinoxaline derivatives with various structural motifs for exploring the desired activity. From this initial library, we have observed few derivatives showed significant activity against different strains.

  • Young Researchers Forum Day 3
Location: Melia Avenida America
Speaker

Chair

Osama Ibrahim

Bio Innovation, USA

Speaker

Co-Chair

Helen McCarthy

Queen’s University Belfast, UK

Session Introduction

Stephen Loughran

Queens University Belfast, Northern Ireland

Title: Development of a peptide-based, multifunctional gene delivey vector for metastatic prostate cancer

Time : 13:55-14:10

Speaker
Biography:

Stephen Loughran was awarded a First Class Masters in Pharmacy Hons by Queen’s University Belfast in 2011. He is currently in his final year of a PhD research project which focuses on the design of multifunctional peptide vectors capable of delivering plasmid microRNA to metastatic prostate cancer. Stephen has two publications to date.

Abstract:

RALA is a 30mer, arginine-rich, amphipathic peptides with both cell-penetrating and endosomolytic properties. When mixed with plasmid DNA it condenses to form small, serum-stable nanoparticles which, when administered in vivo, are capable of transfecting cells. However, bioavailability in vivo was limited to the lungs and liver of treated mice. In order to improve nanoparticle pharmacokinetics, polyethylene glycol (PEG) 5K was conjugated to the C-terminus of the RALA peptide and the resulting conjugate (RALA-P) was characterized in vitro. Disappointingly, activity in vitro was nullified following addition of PEG which lead us to adopt an alternative strategy that involved mixing of RALA-P with native RALA at various w/w ratios in an attempt to restore cellular level activity without compromising pharmacokinetic benefits instilled through the addition of PEG. The resulting nanoparticle exhibited improved salt stability at physiological concentrations of NaCL and was also capable of transfecting cells in vitro. To test biodistribution of the modified nanoparticle, various w/w ratios of RALA/RALA-P containing plasmid fire-fly luciferase were administered to tumour-bearing mice in order to determine whether introduction of PEG in this way could enable transfection in vivo, augment accumulation in the tumour by EPR and reduce accumulation in off-target organs. The results demonstrate a significant reduction in accumulation in the liver and lungs of treated mice and an increase in tumour expression for RALA/RALA-P nanoparticles as compared to RALA only.

Hinojal Zazo Gamez

Universidad of Salamanca, Spain

Title: Gold nanoparticle for macrophage targeting of stavudine

Time : 14:10-14:25

Speaker
Biography:

Zazo H is Licensed in Pharmacy and Post-Graduate in design, manufacture and testing of pharmaceuticals by the University of Salamanca, Spain. Nowadays, she is doing the PhD in pharmaceutical technology, in the same univeristy funding by the Spanish goverment, and she has done a research stay in the Department of Medicine III, RWTH Aachen. She is currently working as Assistant in the Department of Pharmacy and Pharmaceutical Technology, University of Salamanca.

Abstract:

Globally, there are millions of people living with HIV. Although the curret treatment allows controlling the infection, drugs do not efficiently reach target cells such as macrophages which serve as a depot for HIV. It has been proposed drug delivery systems such as nanoparticles to increase drug intracellular penetration. By this way, stavudine gold nanoparticles have been developed and their upke by human primary macrophages has been studied. The coupling of stavudine to the nanoparticles was checked by UV-Vis spectroscopy and zeta potential. Human primary monocyte-derived macrophages were incubated for 24 hours with different concentrations of stavudine gold nanoparticles. Nanoparticle concentrations evaluated for the cellular viability ranged from 0.025 to 25 µg Au/mL with only the highest concentration being slightly cytotoxic for the cells. Their uptake by the cells was studied using Transmission Electron Microscopy (TEM), the intracellular concentration of nanoparticles using Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) and the stavudine uptake was quantified indirectly by Ultra-Presure Chromatography UV spectrosopy (UPLC). The absence of a peak at 530 nm, characteristic of naked gold nanoparticles, in the stavudine-gold nanoparticles spectrum together with the significant change in the ζ-Potential displayed the presence of stavudine coupled to nanoparticles. ICP-MS-based intracellular quantifications of nanocarriers revealed the influence of the nanoparticles concentration in the kinetic of the uptake. UPLC-UV results show that the stavudine uptake after 24 h is deeply higher using gold nanoparticles as carriers. Therefore, stavudine gold nanoparticles, represents a novel nanotechnological strategy to target macrophages, which are of potential interest for HIV therapy.

Speaker
Biography:

Shrawan Baghel is currently doing PhD in “Novel technologies and optimized formulations for delivery of solid dispersion of BCS class II drugs”at Pharmaceutical and Molecular Biotechnology Research Center (PMBRC), Waterford Institute of Technology. He is the winner of Science Foundation Ireland scholarship for this project in collaboration with Synthesis and Solid State Pharmaceutical Centre. The main aim of this project is to gain an insight into the mechanistic and molecular aspects of solid disperison prepared by spray drying, hot melt extrusion and supercritical fluid process using DSC, XRD and NMR.

Abstract:

Amorphous solid dispersions have shown the potential to offer higher apparent solubility and bioavailability of BCS class II drugs. Drug stability, drug-polymer miscibility and drug supersaturation are the fundamental requirements for the successful design and development of such systems. The main objectives of this work are to study amorphous drug crystallization kinetics, assess a theoretical approach for the estimation of drug stability, drug-polymer interaction and miscibility on the basis of Flory-Huggins (F-H) theory and the role of polymer in maintaining drug supersaturation in dissolution media. Firstly, the relevance of fragility and glass forming ability to recrystallization of amorphous drugs is assessed. Secondly, the non-isothermal crystallization kinetics of model systems was also analysed by statistically fitting the crystallization data to 15 different kinetic models and the relevance of model-free kinetic approach has been established. Thirdly, a comprehensive investigation of binary and ternary F-H theory of amorphous solid dispersions of model drugs and polymers was conducted using modulated differential scanning calorimeter, dynamic vapour sorption and X-ray diffraction. The simplified relationship between F-H interaction parameter and temperature was established. This enables us to generate free energy of mixing curves at different temperature and finally the spinodal curve. Furthermore, a three-component F-H model was employed to analyse the moisture sorption behaviour of solid dispersions. It is also used to estimate the F-H interaction parameter of drug and polymer in the presence of moisture since it does not require a priori knowledge about binary interaction parameters between drug and polymer. Finally, the role of polymers in generating and maintaining drug supersaturation in dissolution media has also been investigated. Thus, this research work involves a multidisciplinary approach to establish crystallization tendency/kinetics and F-H theory as stability predictors for amorphous drug formulations.

Speaker
Biography:

Muhammad Irfan Alam is a PhD student at the University of Sunderland, UK. Research project is about “Mucoadhesive and mucopenetrative micro- and nano-particulate drug delivery systems of antibiotics to target Helicobacter Pylori in stomach”. I have completed M.Phil, microbiology, in 2009 and worked as a lecturer in Pak International Medical College for two years.

Abstract:

Helicobacter pylori in stomach is considered as one of the major challenges for the clinicians in terms of resistance. Due to emergence of resistant strains 60-70% of eradication rate is decreased with conventional triple therapeutic regimen. Short resident time of anti Helicobacter pylori drug also leads to failure in complete eradication of the microbe. In the current study, the use of furazolidone mucoadhesive formulations (for local drug delivery approach) to increase the residence time of this antibiotic was studied to overcome above mentioned shortcomings. Two different approaches of mucoadhesive formulation were optimized in terms of residence time and pH of the surrounding environment to attain the desired drug concentration for effective length of time. One of the approach used comprise of polymer coated microparticles and the other consists of mucoadhesive liposomes. Chitosan was used as a mucoadhesive polymer in both approaches and the formulations were investigated on two different pHs. For liposomal mucoadhesion affectivness, fluorometry assay was performed by using coumarin-6 as Fluorophore and the results were further confirmed by the florescence microscopy. Colorimetric method with Periodic Acid Schiff (PAS) Staining of sigma mucin type I was used for microparticles mucoadhesion analysis. In liposomal formulations, 23% mucoadhesion was observed after 6 hours at pH 1.3 (Figure 1a) and 59% mucoadhesion after 6 hours was detected at pH 4.5 (Figure 1b). In the case of microparticles, concentration of cross linking agent (glutaraldehyde, GTA) used was also a determining factor of mucoadhesion in addition to the pH effect. Increase in the concentration of glutaraldehyde have negative impact on mucoadsorption however, increase in pH increase mucoadhesion and vice versa (Figure 2).

Speaker
Biography:

Anton Aleksashkin has completed his Master’s degree from Lomonosov Moscow State University (MSU). He is a PhD student of Lomonosov MSU in the Faculty of Chemistry and a research fellow in BIND RUS.

Abstract:

Numerous diseases ranging from neurodegenerative to some types of cancers are associated with overproduction of reactive oxygen species. Injection of antioxidants could decrease oxidative stress. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, are the most effective antioxidants in nature and could be used to slow oxidative stress. Unfortunately, injection of native enzymes is not effective due to their rapid elimination and instability in blood. Nanoparticles called “nanozymes” based on block-ionomer complexes of negatively charged proteins with positively charged block-copolymers (in particular, polylysine-polyethyleneglycole, PLL-PEG) were previously developed to encapsulate SOD. These cross-linked particles – nanozymes-1 have nanoscale size and preserve specific activity. However, fast release of enzyme from complexes leads to fast elimination from the body. In this presentation, novel type of nanozymes-2 will be discussed. Second negatively charged block-copolymer (poly(glutamic acid)-polyethyleneglycole (PGlu-PEG) was used, and protamine was used instead of PLL-PEG. We were able to increase the reaction yield from 5% to 45%. Developed particles have neutral charge, 50 nm hydrodynamic diameter while nanozymes-1 have slightly positive charge and 40 nm hydrodynamic diameter. Pharmacokinetic experiments showed remarkably increased T1/2 and AUC of double nanozymes versus both standard nanozymes and native SOD. To evaluate therapeutic efficiency of nanozymes, rat spinal cord injury model was used. Recovery of rats was investigated with MRI imaging and BBB-test. Animals that were injected with nanozymes-2, had significant higher scores in BBB-test and lower volume of damage. Thus, easy, scalable method to encapsulate antioxidant enzyme, SOD, was developed.

Speaker
Biography:

Gino Karlo L. Delos Reyes is a second year Chemical Engineering PhD student in Dr. Fenniri’s Supramolcular Nanomaterials Lab at Northeastern University. Gino Karlo studies how novel Rosette Nanotubes can be used as targeted drug delivery agents, especially its applications in cancer. He completed his undergraduate degree at the University of California, San Diego where he received a double major in Chemical Engineering and Biochemistry/Cellular Biology.

Abstract:

Rosette Nanotubes (RNTs), a self-assembled supramolecular nanomolecule composed of fused guanine-cytosine (G^C) bases, provide a novel and innovative modality for the delivery of gene therapeutics to target cells with high efficacy1. This study aims at utilizing RNTs as a nanocarrier platform for the delivery of small interfering RNA (siRNA) to knockdown oncogenic genes to facilitate the elimination of cancer from the body. By conjugating positively charged lysine functional groups to the surface of the RNTs, the nanotubes gain the ability to complex negatively charged siRNA through electrostatic interactions. Through specialized FRET-labeled siRNA and gel retardation assay, we have shown that cationic charges on the RNTs strongly affect the binding interaction and the intracellular delivery of the RNT-siRNA nanocomplex. Furthermore, we have observed higher levels of intracellular siRNA delivery utilizing the RNTs as compared to commercially available Lipofectamine through the use of fluorescently labeled siRNA. Improved gene silencing capabilities were also exhibited compared to commercially available siRNA transfection agents. These data suggest that RNTs has the potential to be both an efficient and biocompatible gene delivery platform.

Speaker
Biography:

Heba Mohamed Abd El-Azim has completed her M.Sc. degree in pharmaceutics from Faculty of Pharmacy, Alexandria University. She is assistant lecturer of pharmaceutics in the Faculty of Pharmacy, Damanhour University. Her master thesis investigated the role of liposomes as nanocarriers in the transmucosal delivery of water soluble drugs. She has published two posters in international conferences and a research article entitled; “Liposomal buccal mucoadhesive film for improved delivery and permeation of water-soluble vitamins” in the International Journal of Pharmaceutics. She gave about 10 seminars and presentations about nanotechnology and drug delivery systems. She attended 11 national and international conferences.

Abstract:

This study aims at improving the buccal delivery of vitamin B6 (VB6) as a model highly water-soluble, low permeable vitamin. Two main strategies were combined; first VB6 was entrapped in liposomes, which were then formulated as mucoadhesive film. Both plain and VB6-loaded liposomes (LPs) containing Lipoid S100 and propylene glycol (~200 nm) were then incorporated into mucoadhesive film composed of SCMC and HPMC. Results showed prolonged release of VB6 (72.65%, T50% diss 105 min) after 6 h from LP-film compared to control film containing free VB6 (96.37%, T50% diss 30 min). Mucoadhesion was assessed both ex vivo on chicken pouch and in vivo in human. Mucoadhesive force of 0.2 N and residence time of 4.4 h were recorded. Ex vivo permeation of VB6, across chicken pouch mucosa indicated increased permeation from LP-systems compared to corresponding controls. Interestingly, incorporation of the vesicles in mucoadhesive film reduced the flux by 36.89% relative to LP-dispersion. Meanwhile, both films provided faster initial permeation than the liquid forms. Correlating the cumulative percent permeated ex vivo with the cumulative percent released in vitro indicated that LPs retarded VB6 release but improved permeation. These promising results represent a step forward in the field of buccal delivery of water- soluble vitamins.

Biography:

Abstract:

Background: Aromatase is an enzyme that leads the bioconversion of androgen into estrogen, which is a main source for cell proliferation and growth in hormone dependent breast cancer. Letrozole (LTZ) is a third generation potent aromatase inhibitor that is approved by the Food and Drug Administration (FDA) for the management of hormone positive breast cancer. The current formulation (Femara®) lacks an effective bioavailability due to LTZ poor-water solubility and rapid systemic metabolism. Aim: To design and characterize LTZ powdered formulations using two formulation approaches; proniosomes and promicelles. Methods: Rotary evaporator apparatus was utilized to produce promicelles. A total of four formulations were prepared, each with a different drug to surfactant ratio. The formulations were prepared by slurry technique and loaded with LTZ. LTZ promicelles and the generated micelles were characterized using zetasizer, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and ultra-performance liquid chromatography (UPLC). Results: Formulation (3) and (4) loaded with 20% LTZ (w/w) were found to be promising with a particle size of 7466±1145 nm and 8543±915 nm, respectively. The drug content was analyzed through UPLC and was found to be 93.45% and 74%, respectively. LTZ entrapment efficiency was reported highest in formulation (4) with a value of 97.5%. Finally, the images obtained from TEM revealed spherical micelles that were in the micro size, confirming the data from the zetasizer. Conclusion: The promicelles were successfully designed and characterized. Particles were spherical and in the micro size with a high entrapment efficiency, indicating improved physicochemical properties of LTZ.