6 ^th European Biopharma Congress September 18-19, 2018 Amsterdam, Netherlands

Biography:

Dr. Alain L. Fymat is the current President/CEO and Professor at the International Institute of Medicine and Science with a previous appointment as Executive Vice President, Chief Operating Officer and Professor at the Weil Institute of Critical Care Medicine, both Institutes located in Rancho Mirage, California, USA. He was formerly Professor of Radiology, Radiological Sciences, Radiation Medicine (Oncology), and Physics at several U.S. and European Universities (University of California at Los Angeles, University of Southern California, Loma Linda University, California; University of Lille, France). Previously, he was Deputy Director (Western Region) of the U.S. Department of Veterans Affairs, Veterans Health Administration (Office of Research Oversight), and Director of the Magnetic Resonance Imaging Center and for a time Acting Chair of Radiology at its Loma Linda, California Medical Center.

Abstract:

There are approximately 400 known neural disorders, some being due to a disruption or failure of the blood brain barrier (BBB) such as, e.g., meningitis, epilepsy, multiple sclerosis, prion and prion-like diseases (Parkinson's, Alzheimer's), HIV encephalitis, and systemic inflammation (sterile or infectious). As a consequence of the growing aging population, many such neurodegenerative diseases, cancer, and infections of the brain will become more prevalent.  Unfortunately, the developmental process for new drugs has not kept pace with progress in molecular neuroscience because most of the new drugs discovered are unable to cross the BBB. This clinical failure may be largely attributed to a lack of appropriate drug delivery systems. Of interest here are those disorders requiring treatment by delivery of nanobiotechnology (NBT)-based drugs through the BBB - one of the most promising applications in clinical neuroscience. Nanoparticles, utilized as drug delivery agents, could potentially carry out multiple tasks in a predefined sequence. They can be effective careers in delivery of conventional drugs, recombinant proteins, vaccines, etc. The following nanotechnologies  are available: liposomes, peptides, radiolabeled polyethylene glycol coated hexadecylcyanoacrylate nanospheres, Polyalkylcyanoacrylate or poly-lactic-co-glycolic acid (PLGA) nanoparticles with polysorbate 80 or poloxamer, and magneto-electric nanoparticles (MENs). Localized and controlled delivery of drugs at their desired sites of action is preferred because it reduces toxicity and increases treatment efficiency. I will discuss the various strategies that have been explored to increase drug delivery into the brain and their attending difficulties, with particular emphasis on NBT-based drug delivery systems.However, although the use of nanotechnology is expected to reduce the need for invasive procedures for delivery of therapeutics, some devices such as implanted catheters and reservoirs will still be needed. Further, there is some concern about the safety of nanoparticle entry in the brain and this needs to be resolved before human use.

Biography:

Debabrata Mukhopadhyay Professor of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, has a joint appointment with the Department of Physiology and Biomedical Engineering and Associate Director of Mayo Clinic Comprehensive Cancer Center for Global Alliances. He has a broad background in tumor microenvironment, with specific training and expertise in key research areas including Cancer, Cardiovascular Diseases, and Diabetes. As a postdoctoral fellow, later as an independent investigator followed by as an Associate Professor at Harvard Medical School, Boston, he carried out angiogenesis and tumor microenvironment related research. After moving to Mayo Clinic as a Professor and also as Directors of both Tumor Microenvironment and Nanomedicine programs, he has been supervising additional research areas including stellate cell biology, new drug delivery systems and trained several young investigators who are now independent faculties in different institutes. Recently, he has received a Tumor Microenvironment Training Grant (T32) from National Cancer Institute. Additionally, he has initiated the biannual Mayo Clinic Angiogenesis and Tumor microenvironment Symposium, which has been widely attended by international and national scientists and also Mayo Clinic and University of Minnesota Nanotechnology workshops. He has been serving as reviewer for several study sections in NIH, and also international funding agencies and also participating as editorial board members of well received journals including Cancer Research and Nanomedicine.

Abstract:

The current body of works suggest that most of the axon guidance proteins interplay with vascular system that leads to vascular development and abnormalities of those pathways usually cause several pathological consequences including cancer. The axon guidance molecules and their receptors are often incongruously expressed in cancers however the molecular pathways of those axon guidance proteins in the tumor cells related to tumorigenesis processes need deeper evaluation. Neuropilin-1 (NRP1), a non-tyrosine kinase receptor, originally discovered as one of the axonal guidance receptor, is overexpressed in several cancers including renal, pancreatic and lung cancers. Originally, our laboratory demonstrated that inhibition of NRP1 expression can lead to differentiation of tumor cells and growth inhibition in renal cell carcinoma and later other laboratories also demonstrated the similar observation on different tumor types including melanoma and brain tumors. Interestingly, our recent data defined a differential role of NRP1 on tumorigenesis, depends upon genetic status of KRAS in the tumor cells. More in depth signaling pathways and its intricacy with respect to drug development will be discussed in this meeting.

Biography:

Dr. Geert C. Mudde received a Ph.D. in immunology from the University of Utrecht in 1985 and started his international professional career at the Swiss Institute for Asthma and Allergy Research in Davos in 1989. In 1992 he joined the pharmaceutical/biotech industry, where he held several senior management positions at the Novartis Research Institute in Vienna, Austria, the Parke Davis Research Institute in Fresnes, France, Ingenium Pharmaceuticals, Martinsried, Germany, and at igeneon AG, Vienna, Austria. Finally, in 2006, while joining Baxter BioScience in Vienna as interim manager, Dr. Mudde co-founded the biotech company f-star Biotechnology, where he served as “Chief Scientific Officer” from 2007 to 2009. In 2009, together with Christof Langer, he started to develop the S-TIR™ technology platform for human specific therapeutic vaccines which led to the foundation of S-TARget therapeutics GmbH in 2010. Since then he serves as CSO and managing director for S-TARget therapeutics as well as for the S-TIR™ technology spin-off companies OncoQR ML GmbH and TYG oncology Ltd., which were both founded in 2013

Abstract:

Using the S-TIR™ technology platform for human specific therapeutic vaccines OncoQR ML has developed two prototype vaccines for treatment of pancreatic cancer (TYG100) and breast cancer (OQR200). Vaccines derived from this platform consist of 2 modules, the disease specific module, “immunogen” and the generic module, “warhead”, which directs the vaccines to CD32 on antigen presenting cells, especially pDCs and B cells. The immunogen in oncology is a tumour associated auto-antigen, against which under normal conditions no clinically relevant immune responses can be induced. We will present conclusive proof that it is finally possible to overcome all the tricks of cancer cells to prevent therapeutic immune responses. No more need for bulk infusion of very expensive and artificial monoclonal antibodies, which either try to mimic tumour specific B cell responses (e.g. Herceptin and Perjeta) OR try to activate cytotoxic T cells, that by chance may also kill tumours (e.g. Opdivo, Yervoy, Keytruda). S-TIR™ vaccines fully activate both arms of the patient’s own immune system resulting in tumour specific polyclonal IgG responses simultaneously with the generation and activation of tumour specific cytotoxic T cells. The responses are reversible and boostable, thus allowing fine-tuning of the clinical responses on a patient to patient basis. S-TIR™ vaccines in contrast to the current checkpoint inhibitors do not induce autoimmune disease and are tumours specific

Biography:

Dr. Krishna is currently Professor and Director of Pharmacology at the College of Osteopathic Medicine, Touro University in Nevada. He obtained a Bachelor of Science (First Class Honors) in Pharmacology and Physiology and a Doctor of Philosophy, Medicine (OB/GYN/Pharmacology) from Monash University in Australia. Dr. Krishna also teaches for the Step 1 USMLE and COMLEX reviews for Kaplan Medical throughout the United States and in UAE, Europe, Saudi Arabia, India, Mexico and the Caribbean. He has been teaching online for Kaplan University for over 7 years and is the contributing author for Kaplan Medical’s Pharmacology Review Book. He has contributed to numerous publications and is a member of a number of organizations including Fellow-American College of Clinical Pharmacology.

Abstract:

During pregnancy psychiatric disorders may occur requiring appropriate therapy. These conditions may also be preexisting which require careful diagnosis and monitoring.

While it is essential to treat such conditions, pregnancy limits the use of psychotropic drugs due to potential adverse fetal outcomes and possibly teratogenicity. Understandably improvement of the disease state may provide benefit to the developing fetus.

Recent studies show that up to 20% of women suffer from mood or anxiety disorders during pregnancy. Depression and anxiety during pregnancy have been associated with a variety of adverse pregnancy outcomes. Women who suffer from psychiatric illness during pregnancy are less likely to receive adequate prenatal care and are more likely to abuse alcohol, tobacco, and other substances known to adversely affect pregnancy outcomes. IUGR, low birth weight and fetal growth retardation in children born to depressed mothers have been documented.

Preterm delivery is another potential complication with an increased risk of pre-eclampsia, operative delivery, and infant admission to a special care nursery for a variety of conditions including respiratory distress, hypoglycemia, and prematurity.

A number of non-pharmacological options are available including cognitive behavioral and interpersonal psychotherapy. Nevertheless a considerable percentage of patients will need pharmacological intervention keeping in mind that a number of psychotropic medications may treat more than one condition.

 This presentation covers maternal mental illness and pregnancy outcome and current therapeutic interventions and guidelines

Biography:

Dr. Ruan is the director of process development and production at PaxVax Inc. She has a Ph.D. degree in biochemical engineering from South China University of Science and Technology. She has extensive experience in bioprocess development, including plant/insect/mammalian cell culture, microbial fermentation, viral vector (Ad4/Ad5/Ad7/HSV/Retroviral) amplification, Virus-like-particle transfection, antibody production, and purification at small and large scale to support preclinical and clinical studies. Dr. Ruan is responsible for developing and manufacturing oral delivery vectors and injectable virus-like-particles for vaccines, as well as researching, evaluating, and optimizing new technology platforms to improve the production scale and stability of the products. 

Abstract:

Chikungunya is a RNA alphavirus that causes arthralgia in its victims.It is spreading by its vector, Aedes aegypti mosquitos throughout the America’s, Asia and Africa.There is no vaccine currently available but a Virus-like-particles (VLP) based vaccine is one of the safest approaches as VLPs lack the genetic material to be infectious.Since VLPs usually adopt native conformation they can present proteins to the immune system much like infectious virus and elicit an efficient immunological response.

PaxVax has licensed the Chikungunya VLP vaccine developed by the Vaccine Research Center (VRC) at the National Institute of Health (NIH). Phase 1 clinical study for the CHIKV VLP vaccine has been completed by VRC and the results indicate that this vaccine is safe, immunogenic and well tolerated.

PaxVax CHIKV VLPs were derived by transient transfection of suspension HEK293 cells with purified plasmid [pCHIKVDNA (Strain 37997); encodes the structural genes of Chikungunya virus and is capable of replicating in E.coli]], further purified by ultrafiltration/diafiltration, anion exchange chromatography, filtration and aliquot into vials for injection.The presentation shows the challenges encountered for the CHIKV VLP transient transfection, scale-up in bioreactor and purification process development. Polyethylenimine (PEI, linear polymer, 25kDa) mediated chemical transit transfection and electroporation transient transfection were evaluated for the scalability and yield.The scalability of the transient transfection process and residual PEI concerns were addressed. Disposable and scalable processes are developed for further clinical development and FDA licensure.

Biography:

Prof. Dr. Oliver G. Schmidt is the Director of the Institute for Integrative Nanosciences at the Leibniz IFW Dresden, Germany. His interests bridge across several disciplines, ranging from nanomaterials and nanoelectronics to microfluidics, microrobotics and  biomedical applications. He has received several awards: the Otto-Hahn Medal from the Max-Planck-Society in 2000, the Philip-Morris Research Award in 2002, the Carus-Medal from the German Academy of Natural Scientists Leopoldina in 2005, and the International Dresden Barkhausen Award in 2013. Most recently, he was awarded the Gottfried Wilhelm Leibniz-Prize 2018 of the German Research Foundation. The Leibniz-Prize is the most important research award in Germany and recognizes his outstanding work in the investigation, manufacturing and innovative application of functional nanostructures.

Abstract:

Nanomembranes are thin, flexible, transferable and can be shaped into 3D microtubular devices. This makes them attractive for a broad range of applications and scientific research fields ranging from novel hybrid hetero structure devices to ultra-compact 3D systems both on and off the chip. If nanomembranes are differentially strained they deform themselves and roll-up into microtubular structures upon release from their mother substrate. Rolled-up nano membranes can be exploited to rigorously compact electronic circuitry into microtubular systems [1]. As rolled-up microtubes can be easily tuned into the size range of single cells, they are perfectly suited to study single cell behaviour in sensitive yet fully integrative lab-in-a-tube systems [2,3]. As off-chip components they address exciting environmental and biomedical applications.  For instance, if magnetic tubes or helices are combined with spermatozoa, such biomagnetic cellular organisms offer new perspectives towards assisted reproduction technologies and drug delivery protocols [4-6]. However, while such micrometer sized robots show great potential for medical applications they face equally big challenges when considering in-vivo operation .

Biography:

Giulio Tarro graduated from Medicine School, Naples University (1962). Research Associate, Division of Virology and Cancer Research, Children’s Hospital (1965-1968), Assistant Professor of Research Pediatrics, College Medicine (1968-1969), Cincinnati University, Ohio. Oncological Virology Professor, Naples University (1972-1985). Chief Division Virology (1973-2003), Head Department Diagnostic Laboratories, (2003-2006). D. Cotugno Hospital for Infectious Diseases, Naples; Emeritus, 2006 -. Since 2007 Chairman Committee of Biotechnologies and VirusSphere, World Academy Biomedical Technologies, UNESCO, Adjunct Professor Department Biology, Temple University, College of Science and Technology, Philadelphia, recipient of the Sbarro Health Research Organization lifetime achievement award (2010). His researches have been concerned with the characterization of specific virus-induced tumour antigens, which were the "finger-prints" left behind in human cancer. Achievements include patents in field; discovery of Respiratory Syncytial Virus in infant deaths in Naples and of tumor liberated protein as a tumor associated antigen, 55 kilodalton protein overexpressed in lung tumors and other epithelial adenocarcinomas.

Abstract:

The compuond EMEB has got a definite anti-Rhinovirus activity on both HRV14 (group A) and HRV39 (group B). The specific activity is lower than that found for Pirodavir used as a positive control, but, since the cytotoxic activity of EMEB on human HeLa cells is more favourable than that of Pirodavir (50 µg/ml against 3 µg/ml), the final Protection Index is higher for EMEB (> 700) as compared to Pirodavir (250). EMEB seems to be stable in aqueous solutions, since its activity after 10 days was unchanged. When EMEB is challanged with Rhinovirus infected HeLa cells during the whole reproduction cicle, its antiviral activity remains evident and strong even after 18 hours from infection. This fact is important because it means that the compound keeps functioning even when the viral infection is already in progress; this finding makes us to hypothesize that the compound EMEB could act not only as a prophylactic agent against the common cold, but also as a therapeutic drug in patients who already show the disease symptoms (at least within the first 24 hours from the start of symptoms). These last statements must be confirmed with assays on the mechanism of action of the compound, by analysing its adhesion to the cell virus internalization into the cells, the viral uncoating, transcription and translation, and finally on viral morphogenesis.

Biography:

Takashi Takahashi is a professor of Medicinal Chemistry at Yokohama University of Pharmacy, Japan. He has his expertise in Natural Products and Medicinal Chemistry of drug development

Abstract:

Automated synthesis and flow chemistry have attracted a great deal of attention in recent years because these process improve both the reproducibility and reliability of synthesis.¹ Development of automated synthetic procedures and storage of relevant digital data allow anyone to reproduce the same results anytime and anywhere using the same apparatus and reagents. As a result, synthetic chemists can spend more time on advanced and challenging problems. Automated synthesis and flow chemistry often enhance the safety profile of the synthetic processes.² Flow chemistry is effective for the hazardous reactions using toxic reagents or high pressure gases. Herein, we report the automated synthesis of taxol³, enediyne⁴, lewisX⁵and ketopiperazine analogues and the flow synthesis of peptides⁶ and aliphatic aldehydes⁷.

Biography:

Dr Yibin Feng is currently an Associate Professor cum Associate Director in School of Chinese Medicine, the University of Hong Kong. Dr. Feng awarded Bachelor degree in Chinese Medicine from Yunnan University of Chinese Medicine, China. He awarded his PhD degree in molecular medicine from Hokkaido University School of Medicine and finished postdoctoral research in the same University in Japan. Dr. Feng’s research interest focuses on clinical and experimental study for cancer, diabetes, hepatic and renal diseases by using recently developed techniques. He has awarded various research grants and has published over 300 publications in these areas and the citation of the SCI papers in total is 5878 in the past 5 years. He has also served as editor and reviewer for over 60 international journals

Abstract:

Facing complicated diseases and unmet medical needs, drug discovery and development from Chinese medicines should have new strategy. There are about 25% modern drug inspired from traditional medicine including Chinese Medicine. The way of drug discovery and development in past 100 years is from natural rescouses to chemical sythsesis, but no matter natural compounds or sythsized compounds for drug discovery and development are more and more difficult. Not only experinced natural materials, but also wisdom and knowlege in traditional medicine may help form new strategy to discover new drug. It is known that 25% modern drugs were inspired from traditional medicine. It has been intensively studied a lot about natural resourse in terms of chmical and pharmacological profiles. So far, over 10000 single compounds were isolated from Chinese medicines (Chinese medicinal plants, animal parts and minerals) among which some have been identified as new drugs such as ephedrine, artnisinin and asenic trioxide etc., while others are promissing drug candidates suggesting Chinese medicines are still an important resource for new drug discovery. It is more amazing if we watch composite formulae, they are over 100000 in total. Clinically, Chinese medicine mainly use composite formulae to treat varouse diseases, especially complicated diseases. Recently, both experimental and clinical studies showed Realgar-indigo naturalies, Qili Qaingxin cupsules and Compound Danshen Dripping Pills are promising formulae for treatment of acute promyelocytic leukemia, chronic heart failure and coronary heart disease. Actually, Western medicine also offen use combination therapy for diseases treatment in clinical setting, such as cancer, hypertension and AIDS etc.. To this goal, we developed a comprehensive, dynamic and specific strategy for drug discovery for cancer and metabolic diseases as one attempt. This presentation will talk about drug discovery from single compounds to multiple components as drug candidates in Chinese medicine by recent developed technologies. The research was financially supported by grants from the RGC GRF, Hong Kong SAR of China (Project codes: 764708, 766211, 17152116), ITF grant (Project code: 260900263), HA Chinese Medicine grant (Project code: 200006345), Donations for Wong’s molecular cancer research in Chinese medicines (Project code: 200006276), the Gaia Family Trust (Project code:200007008) and Vita Green Health Products Co., Ltd. (Project cord: 200007477), and Hong Kong Government Matching funding (Project codes: 207040314, 207060411) as well as industry contract grants (Project codes: 260007482, 260007830).

Biography:

Heike Schön - Managing Director at LUMIS International GmbH

Heike Schön, based in Germany, is co-founder and Managing Director of LUMIS International GmbH.

She has worked in leading positions in clinical research for more than 20 years. Her experience ranges from conducting national and international Phase I clinical trials all the way to registration and post marketing activities as well as business development within contract research organizations (CROs) and the biotechnology industry. Her previous positions included operational and general management. She holds a master’s degree in psychology and a master’s degree in business administration.

Abstract:

The implementation of the new ICH E6 R2 GCP guideline has created confusion, contradictory opinions about what is necessary to be implemented as Sponsor oversight in clinical trials to fulfill the requirements. Sponsor oversight in general is not new, of cause, but the details to mandatory perform oversight activities and to manage compliance for all clinical trial activities have raised  lots of discussions with different opinions and solutions.

One important step in Sponsor oversight is the selection and management of CROs and vendors. The key in CRO/vendor-selection is not only the experience with the specific indication of the CRO, however of same importance is to consider the company cultures to achieve the best alignment within the two or more parties and to define clear responsibilities and expectations.

Finally when it comes to define the different involvement of the stakeholders in a clinical trial the legal aspects have to be carefully considered, not only for the sponsor-vendor relationship but also the site contracts and the different requirement of the respective countries within Europe.

Another challenge for the majority of the smaller sponsors is the set up and maintenaince of clinical trial oversight management and the use of effective tools, to implement a clinical quality management sytem and to train clinical development department team.

Biography:

Jun Xu, a professor of Medicinal and Computational Chemistry at Sun-Yat-Sen University (SYSU), has completed his PhD from University of Science & Technology of China and postdoctoral studies from Australian National University and McGill University. He is the founding Director of SYSU Research Center for Drug Discovery (RCDD), which consisits of Bio/Chemo-informatics lab, Drug Design lab, Phyto/Medicinal Chemistry lab, Structure biology lab, and Drug Screening lab. He is also the adjunct Professor of University of Pittsberg (Pittsberg, USA) and RMIT Univeristy (Melbourne, Australia). He has published more than a hundred papers in peer-reviewed and reputed journals, and served as an editorial board member of a number of reputed international journals.

     Prof. Xu’s research involves in chemistry, pharmaceutical sciences, and informatics. Since the last century, I have been developing algorithms for chemoinformatics/ bioinformatics & pharmaceutical innovations, such as GMA (substructure/superstructure search, 1980s) CPA (fuzzy graph algorithm for protein structure determination from multi-dimensional NMR, 1990s), SCA (clustering large compound libraries, 2000s) and DLI algorithm (drug-like index, 2000s); WEGA (3D molecular superimposing, 2010s) DSGA (de novo frequent substructures recognition, 2010s). With these methods, his team discovered many drug leads against inflammation, virus, cancer and metabolic diseases. The lead compounds against nasopharyngeal carcinoma have entered the pre-clinic studies. He is the inventor of more than 20 patents. Website: www.rcdd.org.cn.

Abstract:

This talk introduces a de novo chemotype (substructure) generation algorithm (DSGA) that derives frequent substructures in order to avoid the subjectivity of empirical method, and avoid the meaningless substructures generated from algorithmic approaches by statistical analyses. DSGA derives frequent chemical substructures (FCS) from a large compound library. In a FCS, substructures are not inter-included. When the library is big enough to represent the chemical diversity, such as ZINC database (27 million medicinal compounds), the resulting FCS is termed as the FCS dictionary (FCSD) for drug-like compounds. For a focused compound library (FL), DSGA can derive a focused FCS (fFCS) from FL. fFCS can be used as structural descriptors for focus library SAR studies.

Six focused libraries against targets PDE4D, mTOR, HDAC1, DPP4, BACE and ALR2 were tested with DSGA approach. Using the fFCSs as structural descriptor sets, six virtual screening models were generated to predict ligands against the targets, the prediction accuracies are greater than 90%.

Three methods were proposed to assembly drug-like molecules from substructures: (1) using the laws in the nature, such as isoprene rule; (2) organic synthesis rules, such as retro-synthon rules proposed by E. J. Corey; (3) pharmaceutical rules derived from a focused compound library against a specific target. We use DSGA to figure out rules that are used to compose privileged scaffolds by assembling FCS.

It can be chemically challenging to make the compounds proposed by these assembling approaches. By combining DSGA method, bioisoterism method and click chemistry, we generated privileged chemome (substructures/chemotypes) from Hsp90 inhibitor library, then find out available chemical fragments with bioisoterism rules. With SPR technology, we confirmed the fragments that interacted with Hsp90. Finally, we used Click chemistry to assembly the substructures, and produced nanomolar selective Hsp90 inhibitors.

Biography:

Myrthe Trompert – CEO and Dir. Legal Consultant at Salvius Legal B.V.

Myrthe Trompert has a Master's Degree in Law from the University of Amsterdam and has worked in the clinical trial industry for over 25 years. During those years, she has contributed in different strategic, management and business development roles, but in particular gained extensive experience in managing the contracting process for large multi-country studies and providing further customized legal support to the different parties in the clinical trial industry. Myrthe Trompert has worked for Contract Research Organizations such as Parexel, NDDO Oncology (now INC Research/Syneos Health) and PharmaNet (now Inventiv Health Clinical/Syneos Health). At PharmaNet, she held the position of Sr. Legal Counsel, responsible for the regions Europe, Latin- America and Asia. Since 2010, she is CEO of Salvius Legal and made it her mission to assist the different stakeholders in the clinical trial industry to make the contracting part of a clinical trial a manageable and controllable process, by applying efficiencies and creative solutions to improve timelines, while maintaining quality and consistency of the contracts involved.

Abstract:

Further to recent changes in laws and regulations, a sponsor of a clinical trial is increasingly made accountable to ensure compliance and oversight of its clinical trials. The new ICH E6 R2 GCP guideline, but for instance also the new General Data Protection Regulation, have increased the responsibilities and obligations of a clinical trial sponsor.

Since many different stakeholders are involved in the conduct of a clinical trial, it can be quite a challenge for a sponsor to maintain control over the conduct of its clinical trial. In addition, in order to avoid other risks when conducting a clinical trial – such as delays, damages or loss of profit – it is important for a sponsor to build a solid foundation for the collaboration between the different stakeholders.

For the above reasons, it is of crucial importance to set up a solid contractual framework and contract management process for each clinical trial. This requires knowledge on international and country-specific laws and regulations, but also requires insight in the roles, responsibilities and risk posititions of the different parties that are involved in the clinical trial, such as Contract Research Organizations, vendors and investigational sites. The presenter will discuss important considerations in this respect.   

Biography:

Heike Schön - Managing Director at LUMIS International GmbH

Heike Schön, based in Germany, is co-founder and Managing Director of LUMIS International GmbH.

She has worked in leading positions in clinical research for more than 20 years. Her experience ranges from conducting national and international Phase I clinical trials all the way to registration and post marketing activities as well as business development within contract research organizations (CROs) and the biotechnology industry. Her previous positions included operational and general management. She holds a master’s degree in psychology and a master’s degree in business administration.

Abstract:

The implementation of the new ICH E6 R2 GCP guideline has created confusion, contradictory opinions about what is necessary to be implemented as Sponsor oversight in clinical trials to fulfill the requirements. Sponsor oversight in general is not new, of cause, but the details to mandatory perform oversight activities and to manage compliance for all clinical trial activities have raised  lots of discussions with different opinions and solutions.

One important step in Sponsor oversight is the selection and management of CROs and vendors. The key in CRO/vendor-selection is not only the experience with the specific indication of the CRO, however of same importance is to consider the company cultures to achieve the best alignment within the two or more parties and to define clear responsibilities and expectations.

Finally when it comes to define the different involvement of the stakeholders in a clinical trial the legal aspects have to be carefully considered, not only for the sponsor-vendor relationship but also the site contracts and the different requirement of the respective countries within Europe.

Another challenge for the majority of the smaller sponsors is the set up and maintenaince of clinical trial oversight management and the use of effective tools, to implement a clinical quality management sytem and to train clinical development department team.

Biography:

Violina T. Angelova  has completed her PhD in organic chemistry in 2004 from Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Science. She has 22 years of research experience and published more than 29 papers in reputed journals. Current position - Assoc Professor at the Faculty of Pharmacy, Medical University of Sofia.

Abstract:

Melatonin receptor (MT1) is an attractive target for elaboration of new drug candidates, but unfortunately is known to be unstable out of the membrane lipid bilayer which makes the obtaining of a crystal structure by X-Ray diffraction (XRD) an elusive goal. Up to now there is no published real structure, suitable for docking of new ligands targeting this receptor. However, there are lots of models based on the data from crystallized rhodopsin, but they are too artificial for reasonable docking of drug-like candidate molecules. To overcome these drawbacks we built an in silico molecular model of a melatonin receptor in membrane bilayer in water cell, with explicit water molecules. For that purpose we used GROMACS molecular mechanics software with GROMOS force field and TYP3P water model. Calculations were carried out in periodic boundary conditions at 300 K and 1 bar pressure, physiological NaCl content and pH 7.

By the simulation we caught the act of melatonin entering the receptor which enlightened a wide variety of interactions that can facilitate or to disturb the movement of melatonin to the hardly accessible active site of MT1. Ðœolecular docking of the drug like candidates was performed on receptor model. The information can be used along with data obtained from the structure of melatonin-receptor complex to construct new analogs of melatonin, capable not only to activate the receptor but also to successfully manage their way to the MT1 binding site. Application grant: DH13/16, 21.12.2017.

Biography:

Professor Kini completed his PhD from Mysore University and postdoctoral studies in Kyushu University, Japan, and Virginia Commonwealth University, Richmond, USA. He is a Professor in National University of Singapore. He has published over 240 research publications and has 50 patent applications. He is the Editor-in-Chief of Toxins Reviews and edited two monographs and five special issues. He also serving on the editorial board of several other international journals. He was a Chairman/Co-Chairman of a subcommittee of International Society on Thrombosis and Hemostasis. He plays important role in International Proteolysis Society (Vice President) and International Society on Toxinology (Executive Committee). 

Abstract:

Hematophagous insects depend on potent anticoagulant and antiplatelet agents for securing their blood meals. We identified a novel class of thrombin inhibitors, named as Ixothrins, from the salivary gland extracts of ticks. We isolated and characterized Variegin and Avathrin from the salivary gland extracts of tropical bont tick (Amblyomma variegatum). They are among the smallest thrombin inhibitors found in nature. We examined the structure-function relationships of both Variegin, Avathrin and Ultravariegin using a number of mutants. We also determined the X-ray crystal structure of thrombin-Variegin and thrombin-Avathrin complexes. They interact with exosite I, prime subsites and active site of thrombin. Based on the structure as well as the prior knowledge on thrombin inhibitors, we designed several peptides to understand the interaction between thrombin and these inhibitors. These peptides cover a diverse spectrum of potency, kinetics and mechanism of inhibition, including peptides with affinities ranging from low picomolar to nanomolar values, with fast and slow tight binding, displaying competitive and non-competitive inhibition. We evaluated the antithrombotic efficacy (carotid artery thrombosis and stent thrombosis models) and bleeding side effects (tail incision and ear bleeding models) of Variegin in rats and pigs, respectively. The results strongly support the superior antithrombotic efficacy of Variegin with minimal bleeding in comparison with comparator drugs, heparin and hirulog (Bivaluridin or Angiomax®). Thus, ixothrins may have the potential in developing parenteral anticoagulant agents for percutaneous coronary intervention (PCI).

Biography:

Oara Neumann has completed her PhD and Postdoctoral study in Applied Physics at Rice University and MS from Weizmann Institute of Science, Israel, and Bucharest University, Romania. She is a research scientist in Naomi Halas group at Rice University. She holds 12 patents and she has published more than 25 papers in reputed journals.

Abstract:

Multifunctional plasmonic nanostructures have enormous potential in the treatment of solid tumors; however, tracking particles with drug cargo and triggering the release of the cargo in mapped tumors is still impossible. To overcome this challenge we have developed an MRI and fluorescent active nanostructure nanomatryoshka. This new nanostructure with IR plasmonic signatures is composed of a 50 nm Au core surrounded by dye molecules and Gd(III)-DOTA chelate doped SiO₂ inner-shell and an outer Au shell. The experimental results demonstrates an enhanced T₁ relaxation (r₁ ~ 24 mM^-1 s^-1 at 4.7 T) compared to the clinical Gd(III)-DOTA chelating agents (r₁ ~ 4 mM^-1 s^-1). Further, this design preserves the fluorescence signal (65%) after 24 hours of exposure, leading to enahanced fluorescence photostability (23x). This dual-imaging functionality nanosystem increases MRI sensitivity by concentrating Gd(III) ions into the Gd-NMs, reduces the potential toxicity of Gd(III) ions and dye molecules by preventing their release in vivo through the outer Au shell protection, and the terminal gold layer surface can then be functionalized to increase cellular uptake, circulation time, or thermal drug-release properties.

Biography:

Ineke Rijnhout is the Managing Partner at Beyond Tomorrow (www.beyondtomorrow.today) specializing in strategic and operational guidance to biotechnology start-up companies and CROs. With over 20 years of experience, she held a number of senior executive leadership positions at SMEs as well as CROs. She provides expertise to her life-science clients in accessing and raising capital, managing their clinical programs, or identifying partners for licensing deals, M&A and strategic alliances.  Ineke received her master’s Degree in medical sciences from the Faculty of Medicine, University of Leiden, the Netherlands, and has certifications from European Venture Capital Association (EVCA) and Pharmaceutical Licensing.

Abstract:

Senior Management in biotechnology organizations span the gamut of industry expertise from deep academic and research backgrounds to corporate, global bio-pharma skills, and everything else in between.  This internal collective corporate experience and history often drives how a clinical research organization (CRO) partners are eventually selected, and often without considerations to other key imperative elements that determine the best fit, for the immediate as well as the long-term needs of a clinical development program.  The presenters will utilize case-study examples from biotechnology companies in Europe, Japan, and the US to describe how biotechnology companies can increase their chances of success in choosing an appropriate external clinical development partner.  Understanding where blind-spots often occur, how to navigate internal corporate mind-sets, and individual biases will be discussed through case-examples.  Various approaches and solutions will be highlighted, and specifically tailored for the small- to mid-size biotechnology companies.  The presenters will also discuss critical issues in the selection process such as fees, deliverables, timelines, and managing disappointments.

Biography:

Heike Schön - Managing Director at LUMIS International GmbH

Heike Schön, based in Germany, is co-founder and Managing Director of LUMIS International GmbH.

She has worked in leading positions in clinical research for more than 20 years. Her experience ranges from conducting national and international Phase I clinical trials all the way to registration and post marketing activities as well as business development within contract research organizations (CROs) and the biotechnology industry. Her previous positions included operational and general management. She holds a master’s degree in psychology and a master’s degree in business administration.

Abstract:

The implementation of the new ICH E6 R2 GCP guideline has created confusion, contradictory opinions about what is necessary to be implemented as Sponsor oversight in clinical trials to fulfill the requirements. Sponsor oversight in general is not new, of cause, but the details to mandatory perform oversight activities and to manage compliance for all clinical trial activities have raised  lots of discussions with different opinions and solutions.

One important step in Sponsor oversight is the selection and management of CROs and vendors. The key in CRO/vendor-selection is not only the experience with the specific indication of the CRO, however of same importance is to consider the company cultures to achieve the best alignment within the two or more parties and to define clear responsibilities and expectations.

Finally when it comes to define the different involvement of the stakeholders in a clinical trial the legal aspects have to be carefully considered, not only for the sponsor-vendor relationship but also the site contracts and the different requirement of the respective countries within Europe.

Another challenge for the majority of the smaller sponsors is the set up and maintenaince of clinical trial oversight management and the use of effective tools, to implement a clinical quality management sytem and to train clinical development department team.

Biography:

Hiroko Tadano is the Managing Partner at Beyond Tomorrow (www.beyondtomorrow.today) specializing in strategic and operational guidance to biotechnology start-up companies and CROs. With over 20 years of experience, she held a number of senior executive leadership positions at SMEs as well as CROs. She provides expertise to her life-science clients in accessing and raising capital, managing their clinical programs, or identifying partners for licensing deals, M&A and strategic alliances.  Ineke received her master’s Degree in medical sciences from the Faculty of Medicine, University of Leiden, the Netherlands, and has certifications from European Venture Capital Association (EVCA) and Pharmaceutical Licensing.

Abstract:

Senior Management in biotechnology organizations span the gamut of industry expertise from deep academic and research backgrounds to corporate, global bio-pharma skills, and everything else in between.  This internal collective corporate experience and history often drives how a clinical research organization (CRO) partners are eventually selected, and often without considerations to other key imperative elements that determine the best fit, for the immediate as well as the long-term needs of a clinical development program.  The presenters will utilize case-study examples from biotechnology companies in Europe, Japan, and the US to describe how biotechnology companies can increase their chances of success in choosing an appropriate external clinical development partner.  Understanding where blind-spots often occur, how to navigate internal corporate mind-sets, and individual biases will be discussed through case-examples.  Various approaches and solutions will be highlighted, and specifically tailored for the small- to mid-size biotechnology companies.  The presenters will also discuss critical issues in the selection process such as fees, deliverables, timelines, and managing disappointments

Biography:

Heike Schön - Managing Director at LUMIS International GmbH

Heike Schön, based in Germany, is co-founder and Managing Director of LUMIS International GmbH.

She has worked in leading positions in clinical research for more than 20 years. Her experience ranges from conducting national and international Phase I clinical trials all the way to registration and post marketing activities as well as business development within contract research organizations (CROs) and the biotechnology industry. Her previous positions included operational and general management. She holds a master’s degree in psychology and a master’s degree in business administration.

Abstract:

The implementation of the new ICH E6 R2 GCP guideline has created confusion, contradictory opinions about what is necessary to be implemented as Sponsor oversight in clinical trials to fulfill the requirements. Sponsor oversight in general is not new, of cause, but the details to mandatory perform oversight activities and to manage compliance for all clinical trial activities have raised  lots of discussions with different opinions and solutions.

One important activity for Sponsors is to define and implement tools for effective oversight management of their clinical trials, to implement a risk based clinical quality management sytem and to train the clinical development teams.

During the session we will explain the different steps needed to implement an effective oversight quality management system covering the following topics in more details and with case studies:

• Defining a risk based quality management system
• Early implementation of  tools for clinical trial oversight management  (e.g., through key performance indicators)
• Effective communication with all stakeholders

With an early investment  in the beginning of a clinical trial or program and with  careful planning and team education sponsors will be able to perfrom successful risk based oversight management and to keep the required balance between oversight and „micromanagement“ and most important to keep balance with the budget.

Biography:

Hani Zaki is the Managing Partner at Beyond Tomorrow (www.beyondtomorrow.today) specializing in strategic and operational guidance to biotechnology start-up companies and CROs. With over 20 years of experience, she held a number of senior executive leadership positions at SMEs as well as CROs. She provides expertise to her life-science clients in accessing and raising capital, managing their clinical programs, or identifying partners for licensing deals, M&A and strategic alliances. Zaki  received her master’s Degree in medical sciences from the Faculty of Medicine, University of Leiden, the Netherlands, and has certifications from European Venture Capital Association (EVCA) and Pharmaceutical Licensing.

Abstract:

Senior Management in biotechnology organizations span the gamut of industry expertise from deep academic and research backgrounds to corporate, global bio-pharma skills, and everything else in between.  This internal collective corporate experience and history often drives how a clinical research organization (CRO) partners are eventually selected, and often without considerations to other key imperative elements that determine the best fit, for the immediate as well as the long-term needs of a clinical development program.  The presenters will utilize case-study examples from biotechnology companies in Europe, Japan, and the US to describe how biotechnology companies can increase their chances of success in choosing an appropriate external clinical development partner.  Understanding where blind-spots often occur, how to navigate internal corporate mind-sets, and individual biases will be discussed through case-examples.  Various approaches and solutions will be highlighted, and specifically tailored for the small- to mid-size biotechnology companies.  The presenters will also discuss critical issues in the selection process such as fees, deliverables, timelines, and managing disappointments.

Biography:

Flavia Laffleur, is an assistant prfoessorand a senior researcher of Drug Delivery in the Department of Pharmacy at LFU Innsbruck, Austria. Flavia Laffleur published over 68 publications and gave oral presentations on several international conferences. From 2010 until 2013 she completed her doctoral thesis focused on smart drug delivery systems. Since 2013, she is a senior researcher at the Department of Pharmaceutical Technology in Innsbruck. Since 2017, Dr. Flavia Laffleur is a researcher at the MIT, in Boston, Massachusetts. She received several awards, including Lesmüller-Stiftung award and the Galenus Foundation Technology Award. Currently Dr. Laffleur´s research focusses on mucosal drug delivery as well as smart delivery systems to overcome biological barriers

Abstract:

Predominantly, the majority of fungal infections (dermal and nail) are caused by dermatophytes, such as Trichophyton rubrum known as one of the most prominent . Among fungal infections, nail infections or onychomycosis exhibit the most difficulties and limitations in their treatment. Onychomycosis affects around 5-10% of the population in the world. Onychomycosis is a common infection of the nail caused by dermatophyte affecting mostly toenails in adults being associated with limited treatment options. In this study novel dosage forms were prepared and evaluated for their suitability in treatment of onychomycosis. Films were prepared comprising polymeric excipients such as chitosan, (hydroxypropyl)methyl cellulose, hydroxyethyl-cellulose, carboxymethylcellulose according to solvent evaporation method. Developed formulations were evaluated in terms of physical appearance, stability and adhesiveness. Furthermore skin and nail irritation studies were conducted. Five potential formulations (F1-F5) were designed while F1 and F4 exhibited the most promising results in terms of stability with 26 min and 40.67 min, respectively, and suitability in nail application. F1 as the most favorable dosage form revealed with 2.9438 kg/m/s in terms of adhesive force the most adhesive properties in contrast to the other preparations. All formulations were found to be non-skin irritating and safe to use. Taken together, these findings suggest novel designed films containing polymeric excipients as a fruitful platform for the treatment in onychomycosis.

Biography:

Abstract:

The effect of storage conditions showed that the release rate of the drug was significantly increased from tablets that were stored for longer periods at 40 â—¦C. That is to say, drug release was faster at longer storage times (8 > 4 > 2 > 0 weeks) Figure 1(A, B). The increase in drug release is expected to be due to oxidative degradation primarily in the amorphous region of the polymers [3]. Fig. 2 (C, D) demonstrated that there was significant decrease in the drug release rate of the formulations that contained mannitol and DCP. The results in Figure 3 (E,F) indicated the use of vitamin E stabilized PEO and decreased the rapid drug release occurring as a result of the storage time (2, 4, 8 weeks) at 40 â—¦C. The reason behind this phenomenon could be when vitamin E was dispersed in the PEO containing drug, it delayed the penetration of oxygen into the PEO matrix during the storage time 

Biography:

Andrey Nikolaevich Belousov graduate from Kharkov Medical Institute in 1988. Doctor of Medicine degree on speciality - An­esthesiology and Intensive Care since 2004. The title dissertation: “Extracorporal hemocorrection using magnet-controlled sorbent in intensive therapy of intoxication syndromes in patients with hepatopancreatoduodenales dis­eases”. Author a new medecine products – nanotechnology preparations based on magnetite nanoparticles (Fe₃O₄) of the size 6-12 nm (www.nanolab.com.ua): the peroral form - Micromage-B (the biologically active additive officially registration in Ukraine); Magnet-controlled sorbent brand of MCS-B for extracorporal detoxication of biological liquids (officially registration in Ukraine and was allowed for medical practice); NanoBiocorrector for intravenous application – ICNB (intracorporal nanosorbent). A.N. Belousov is author new method of extracorporal hemocorrection using magnet-controlled sor­bent (MCS-B).  Author a new program for estimation degree the severity of the patient. Based on previously developed a universal analytical system of the physiological state of the body (PHUAS) by the author proposed a new automatic program objective assessment of the severity of the patient's condition. Overall, the program can improve health of the population in terms of underfunding by the rapid and objective examination of a large quantity of people. Early on, with the help of the developed program is made possible among surveyed identify risk groups in the severity of general condition, to determine the optimal and effective options for prevention and treatment, saving time and money for the survey, use the data to correlate them with various factors influence of the environment (ecology, nutrition, addictions, drug, vaccine, methods of intensive therapy, pharmacotherapy, etc.). The published more 160 scientific works on results application of nanotechnology preparation in experimental and practical medicine. He has got 7 patents for the invention, 21 collected scientific articles, 68 works in other publications and thesis of reports at international conferences and congresses, including 35 of them abroad (Rumania, Austria, Germany, Czech, Switzerland, Hungary, Denmark, Portugal, Italy, Canada, U.S.A., China, India, and others). Author of the scientific film which focuses on the elaboration of artificial liver device and the development of a new direction in medicine – Nanotechnology. Andrey Belousov was awarded Medical Diploma of Europe “An Honorary Scholar Europe” and R. Koch medal for the scientific achievements, development of a new direction in medicine and elaboration of new method of treatment by means preparations of nanotechnology in 2008. Member of the Ukrainian and Russian Society Nanotechnology. At now Andrey Belousov - the Head of Laboratory Applied Nanotechnologies in Ukraine, DM, Professor of Department Anesthesiology, Intensive Care, Transfusiology and Hematology Kharkov Medical Academy of Postgraduate Education.

Abstract:

The influence of basic physical factors caused by magnetite nanoparticles (constant magnetic field and sorption) on microorganisms by examining the reactions of the intensity of free radical lipid peroxidation (FRLP) and bacteriostatic action was studied. It was well established that the magnetite nanoparticles caused unequal reaction in intensity of FRLP on different groups of microorganisms. It was determined that the most significant factor that influenced on the ultimate indicator of the intensity of luminescence on candida albicans, escherichia coli and pseudomonas aeruginosa was constant magnetic field which induced by nanoparticles. On the contrary, sorption was the most significant factor on staphylococcus aureus. It was found that the rate of consumption of free radicals lipid reduced reliably on all microorganisms after their processing by magnetite nanoparticles. The results of microbiological studies of escherichia coli, klebsiella pneumoniae and staphylococcus aureus showed that bacteriostatic effect was detected after exposure by magnetite nanoparticles. Visually, it was detected by decreasing the number of colonies on the nutritious medium in comparison with the control. It was revealed an interesting fact that saline NaCl, which had previously been processed by magnetite nanoparticles also significantly had a marked bacteriostatic effect on the studied microorganisms. This effect could be explained by mechanism of change the polarization structure water of microorganisms by magnetite nanoparticles. It was discovered that degree of expression of bacteriostatic action which induced by magnetite nanoparticles had correlation with marks of reactions intensity of FRLP. Maximum bacteriostatic effect on staphylococcus aureus was expressed in second variant application of magnetite nanoparticles where mechanism of sorption was more significant than action of the magnetic field. On the contrary, maximum bacteriostatic effect on escherichia coli and klebsiella pneumoniae was revealed in third variant, where time exposition of contact with microorganisms nanoparticles and, consequently, action of a constant magnetic field was determinative.

Biography:

Anteneh Assefa is a proffesor in Department of Pharmacy, College of Health Sciences, Wachemo University

Abstract:

Starch from the tubers of Ethiopian potato (Plectranthus edulis) (Fam. Lamiaceae) has been isolated and examined for its chemical composition, amylose content and physicochemical properties. The yield of starch was about 80.4% on dry weight basis. The proximate composition of the starch on dry weight basis was found to be 0.14% ash, 0.21% lipid, 0.43% protein, and 99.22% starch. The amylose content was 30.6%. Its true density and moisture content values were 1.47 g/ml and 11.2%, respectively. Scanning electron microscopy (SEM) of the starch granules showed characteristic morphology that was by large oblong (elliptical) with some oval-shaped granules. The starch has normal granule size distribution with a mean particle size of 36.20 µm. The DSC thermograms of P. edulis starch obtained from starch-water mixtures (1:1), exhibited higher T₀ (69.2 ^oC), T_p (74.3 ^oC) and T_e (83.3 ^oC) values than those of potato starch. X-ray diffraction pattern of the starch was typical B-type with a distinctive maximum peak at 17.5^o 2θ. The starch possesses higher swelling power and moisture sorption pattern but lower solubility values than those of potato starch at all temperatures studied. Considering the high yield value and some similar physico-chemical properties to those of potato starch, P. edulis (Ethiopian potato) can be explored as an alternative source of starch for various applications

Biography:

Saeed Shojaee  is an professor at Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham, Kent, UK

Saeed Shojaee  is an professor at Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham, Kent, UK

Abstract:

Abstract : Polyethylene oxide (PEO) is one of the hydrophilic polymers that have been extensively used to prepare sustained and modified release dosage forms.The objective of this study is to investigate the effect of vitamin E succinate and different fillers (mannitol and DCP) on release rate stability of highly soluble drug diltiazem HCl containing Polyethylene oxides.

The effect of storage conditions showed that the release rate of the drug was significantly increased from tablets that were stored for longer periods at 40 â—¦C. That is to say, drug release was faster at longer storage times

(8 > 4 > 2 > 0 weeks) Figure 1(A). The increase in drug release is expected to be due to oxidative degradation Primarily in the amorphous region of the polymers¹.

 The results in Figure 2 (B) also showed that there was a significant decrease in the drug release rate of the formulations that contained all concentrations of  Vit E used (1% w/w). In other words, the use of Vit E PEO decreased the rapid drug release occurring as a result of the storage time (2, 4, 8 weeks) at 40â—¦C. The reason behind this phenomenon could be when Vit E was dispersed in the PEO containing drug, it delayed the penetration of oxygen (O2) into the PEO matrix during the storage time¹{Figure2(B)]. These results confirmed by viscosity data which they are shown in Figure (2). As it can be seen from Figure (2) the viscosity of the polyox samples containing Vit E is higher than the same samples without Vit  E. Fig.3 (A,B) shows that there was a significant decrease in the drug release rate of the formulations contained mannitol and dicalcium phosphate (DCP). This can be attributed to an increase in viscosity of gel layer and also they are able to form a complex with a cationic drug.

Biography:

Jana Tchekalarova has completed her PhD in pharmacology in 2004 from Institute of Physiology, BAS. She has 22 years of research experience. Current position - Assoc Professor at the Institute of Neurobiology, BAS, Head of “Behavioral neurobiology” Dept.  An Adjunct Professor at the Section of Biochem, Physiol Pathophysiol in the Med Dept Sofia University. According to Mendeley profile: h-index = 12, publications 51 with IF; citations = 385. More than than 500 citations. She has been serving as an editorial board member of Drug Dev Res, J Neurol Dis Stroke and Asian Counc Sci Editors.

Abstract:

The majority of available literature on experimental animals revealed that melatonin has anticonvulsant action in acute seizures tests with different mechanism of action. An important advantage of melatonin as an add-on option in a therapy of epilepsy is associated with its low toxiticy, antioxidant activity as well as its ability to synchronize disturbed circadian rhythms in epileptic patients.  A series of melatonin analogues, containing indole scaffold, were synthesized and their anticonvulsant activity was tested on ICR mice by measuring the time of three different seizure phases (myoclonic, clonic and tonic) induced by intravenous infusion of pentylenetetrazol (PTZ). The novel melatonin derivatives were synthesized according to the classical method by condensation of hydrazones with 5-methoxyindole-3-carboxaldehyde or 5-benzyloxyindole-3-carboxaldehyde. The hydrazide-hydrazones with indole moyeties were purified by recristalization and the molecular weights were determined, using ES-MS. The compounds were injected intraperitoneally at doses of 30, 60 and 100 mg/kg 30 min before PTZ. The most potent compounds, with significantly increased thresholds for myoclonic, clonic and tonic seizures compared to vehicle were the derivatives with 2-thienyl and p-Cl-phenyl fragments at a dose of 60 mg/kg, which effects was comparable to that of melatonin at the same dose of 60 mg/kg, used as a positive control. None of the compounds displayed neurotoxicity in the rota-rod test. In silico assessment of their BBB permeability indicated them as CNS active agents. Ðœolecular docking was performed into a human gamma-aminobutyric acid (GABA_A) receptor and depicted good binding properties of melatonin derivatives, considered in this study. Based on anticonvulsant screening results these newly synthesized melatonin derivatives will be explored in other seizure tests with different mechanism of action as well as in models of epilepsy. Application grant: National Science Fund of Bulgaria (#

DH13/16, 21.12.2017).

Biography:

Assistant Professor at The Maharaja Sayajirao University of Baroda

Abstract:

Microneedles may be defined as needles that are 10-2000 microns in height and 10-50 microns in width. They are available in the form of an array which consists of a plurality of micron-sized projections typically assembled on one side of a supporting base or patch. Microneedles are the sharp and short needles used for enhancement of transdermal permeation of drugs. Due to their short length, upon application, they do not touch the nerve endings and hence are devoid of pain. Different types of microneedles reported to enhance the transdermal permeation are solid MN, coated MN, hollow MN and dissolving MN. Various materials ranging from metal, silicon, glass, sugars and polymers-biodegradable and non-biodegradable have been used for fabrication of microneedles. The present paper aims to highlight the importance and application of various types of microneedles in transdermal drug delivery. The advantages and disadvantages of the different types of microneedles would be discussed. Depending upon the material used for fabrication, microneedles may be employed for rapid release or sustained release of drug. Microneedles are particularly useful for delivery of biopharmaceuticals like hormones, peptide and protein delivery. A case study involving the use of microneedles for enhancement of transdermal penetration of a drug will be presented.

Biography:

Holder of the First Class Golden Medal for Sciences and Arts and the recipient of the 2010Appreciation State Prize in the realm of Advanced Technological Sciences.Professor Ammar is currently the Chairman, Pharmaceutical Technology Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt; formerly, Dean of the Pharmacy Division, National Research Centre, Cairo, Egypt. He has more than 110 research papers published in international scientific journals. These research papers cover most of the areas related to pharmaceutics, biopharmaceutics and pharmacokinetics. Design of new drug delivery systems is not beyond the scope of his interest.

Abstract:

Nanotechnology is attracting great attention worldwide in biomedicine. Targeted therapy based on drug nanocarrier systems enhances the treatment of tumors and enables the development of targeted drug delivery systems.

In recent years, theranostics are emerging as the next generation of multifunctional nanomedicine to improve the therapeutic outcome of cancer therapy. Polymeric nanoparticles with targeting moieties containing magnetic nanoparticles as theranostic agents have considerable potential for the treatment of cancer.

The use of directed enzyme prodrug therapy (DEPT) has been investigated as a means to improve the tumor selectivity of therapeutics. Magnetic DEPT involves coupling the bioactive prodrug-activating enzyme to magnetic nanoparticles that are then selectively delivered to the tumor by applying an external magnetic field.

Gene therapy is an attractive method for meeting the needs for curing brain disorders, such as Alzheimer’s disease and Parkinson’s disease. On the other hand, due to the fact that hepatocellular carcinoma (HCC) is resistant to standard chemotherapeutic agents, gene therapy appears to be a more effective cure for HCC patients.

Ultrasound-mediated drug delivery is a novel technique for enhancing the penetration of drugs into diseased tissue beds noninvasively. This technique is broadly appealing, given the potential of ultrasound to control drug delivery spatially and temporally in a noninvasive manner.

Biography:

I am PhD student in medical phisiology, now my thesis about neuropathy and pain in spinal cord injury patiate, in MSD degree i worked on rats with field of pain and addiction and i published 5 ISI paper in behavior neroscience and other jornals. I expert in some test in animals like; formalin test, Conditioning Place Preference (CPP), T-maze and Tail Flick Test

Abstract:

The nucleus accumbens (NAc) and the ventral tegmental area (VTA) are two major areas for the mesolimbic dopaminergic system which are strongly involved in the development of behavioral sensitization. In the present study, we investigated the role of D1/D2 dopaminergic receptors within the NAc or VTA in response nsensitization to morphine by the tail-flick test as a model of acute pain. Sensitization was induced by subcutaneous (SC) injection of morphine (5 mg/kg), once daily for three days followed by 5 days free of drug. After the sensitization period, antinociceptive responses induced by an ineffective dose of morphine (1 mg/kg; SC) were obtained by the tail-flick test, and represented as maximal possible effect (%MPE). In experimental groups, D1 and D2 receptor antagonists, SCH-23390 and sulpiride (0.25, 1 and 4 µg/rat), were separately microinjected into the NAc or VTA, 10 min before morphine administration during the sensitization period, respectively. Results showed that injection of morphine during the sensitization period (development of sensitization) increased %MPE of the ineffective dose of morphine from 2.43±1.4% in naive to 47.75±4.01% in sensitized animals (P<0.001). Unilateral microinjections of different doses of the D1/D2 receptor antagonists, SCH-23390 and sulpiride, into the NAc dose-dependently decreased %MPEs in morphine-sensitized animals. Nonetheless, %MPEs were only affected by intra-VTA administration of SCH-23390 in morphine-sensitized animals (P<0.05). Our findings suggest that both the D1/D2 dopamine receptors in the NAc and the D1 receptors in the VTA may be of more important in the development of sensitization to in rats.

Biography:

Abstract:

Policosanol (POL) is a hypocholesterolemic drug of natural origin and has been shown to reduce

circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) in healthy subjects. Recently,

we have reported that POL can attenuate aortic calcification in diabetic dyslipidemic rats; however, the

underlying mechanism is not fully elucidated. We aimed to investigate the effect of POL on aortic calcification and if PCSK9 has a contributory role, and also to examine whether combination of POL with pentoxifylline (PTX), as antitumor necrosis factor alpha (TNFα) would offer additional benefits. Thirty adult male New Zealand rabbits weighing 1.5–2 kg were randomly assigned into five groups. One group received standard chow diet and served as normal control group (NC). The other four groups received 0.5% w/w cholesterol rich diet for 12 weeks and concurrently treated with either placebo, POL, PTX orcombination of POL and PTX. Sera samples and aortic tissue were collected for biochemical

measurements and histological assessment. Rabbits fed a cholesterol rich diet demonstrated dyslipidemia, increased inflammatory state and elevated serum levels of PCSK9, compared to NC group.

Aortic calcification was evident in dyslipidemic rabbits, represented by increased calcium deposition and

osteopontin (OPN) expression in aortic tissue, along with elevated serum levels of alkaline phosphatase

(ALP) and osteocalcin (OCN). Dyslipidemic rabbits showed a significant up regulation of wingless type

MMTV integration site family 3A (Wnt3a) and bone morphogenetic protein 2 (BMP 2) genes in their aortic

tissue. POL significantly reduced circulating PCSK9 levels, suppressed calcification markers and

attenuated aortic calcification. Combination of POL with PTX alleviated aortic calcification to greater extent than either monotherapy, which may be attributed to further suppression of PCSK9 and calcification markers. These findings suggested that POL exerted anti calcifying effect partly via inhibition of PCSK9. Combination of POL and PTX offered additional benefits and might represent a promising therapeutic option for aortic calcification.