Day 2 :
Cardiff University. UK
Keynote: Overcoming Cellular Barriers for Drug Delivery: Opening Endocytic Gates and Pathways for Intracellular Targetting
Time : 09:30-10:10
Arwyn gained his PhD in protein biochemistry and crystallography at Birkbeck College, University of London. Then he undertook postdoctoral positions investigating endocytosis at the University of Liverpool and Harvard University, Boston USA. In 2000 he was awarded a European Molecular Biology Organization fellowship to work at the European Molecular Biology Laboratory (EMBL), Heidelberg Germany, and continued at the EMBL when he was awarded an Alexander von Humboldt Foundation Scholarship. He was appointed as Lecturer at the Cardiff School of Pharmacy and Pharmaceutical Sciences at Cardiff University in 2002 where he is now a Professor in Membrane Traffic and Drug Delivery.
Targeting a disease process inside a cell with biopharmaceuticals still represents a major challenge, not least in overcoming biological barriers such as those posed by the plasma membrane. Investment in this approach is justified when one considers the number individual intracellular targets now available to us as we continue to understand disease processes at the gene and protein level. This is true for many high-burden diseases including cancer, infectious diseases and inherited genetic defects such as cystic fibrosis. Our research is focused on studying endocytosis and specifically on designing methods to analyse individual endocytic pathways to characterise how drug delivery vectors and associated therapeutics gain access to cells. As vectors we have paid particular attention to natural ligands, cell penetrating peptides and antibodies, focusing on their capacity to not only interact with, and enter cells, but then on monitoring their intracellular traffic to reach a final destination. In this lecture I will describe work we have performed focusing on design and characterization of methods to study endocytosis of drug delivery vectors and on recent studies showing how internalisation of plasma membrane receptors can be significantly enhanced, and their normal endocytic routes modified to reach a desired intracellular location. Our involvement in a €30M FP7 Innovative Medicine Initiative (IMI-EFPIA) consortium (COMPACT www.compact-research.org/) will also be discussed. This represents a public-private collaboration between 14 European academic institutes and pharmaceutical companies aiming to improve the cellular delivery of biopharmaceuticals across major biological barriers of the intestine, lung, blood brain barrier and skin.
Kingston University, UK
Keynote: Age-related sight loss: novel drug delivery strategies to the anterior and posterior segments of the eye
Time : 10:10-10:50
Professor Raid Alany has over 25 years of international experience in pharmacy education, pharmaceutics and drug delivery research. His academic journey spans three continents, namely, Asia, Oceania and Europe. He received his PhD in drug delivery from the University of Otago, Dunedin New Zealand in 2001; was appointed as a Lecturer at the School of Pharmacy, The University of Auckland, Auckland, New Zealand. He joined Kingston University London as Professor (Chair) of Pharmaceutics in January 2011 and was appointed as Research Director for the School of Pharmacy and Chemistry in December 2013. Raid is an author on over 200 scientific research publications (papers and abstracts), a book and seven book chapters. Professor Alany acts as Editor-in-Chief for Pharmaceutical Development and Technology, Section Editor for Clinical and Experimental Ophthalmology the official journal of the Royal Australian and New Zealand College of Ophthalmologists; Chief Patron, Drug Development and Therapeutics, a publication of Organization of Pharmaceutical Unity with BioAllied Sciences (OPUBS). He serves on the Editorial Board of the following journals: Current Medical Research and Opinion, BioMed Research International, Journal of Drug Delivery Science and Technology, Current Drug Delivery, Pharmaceutics MDPI, and Drug Delivery Letters. He is the Immediate Past President of the New Zealand Chapter of the Controlled Release Society (NZCRS), Young Scientist Committee of the Controlled Release Society. Raid won several awards such as Microscopy New Zealand Young Scientists Award in 1999 The University of Auckland's Vice Chancellor's Early Career Research Excellence Award in 2003, the Controlled Release Society Veterinary Programme co-chair/ chair Distinguished Service Awards in 2008/2009 and the Spark Ideas Challenge, Uniservices Prize and Chiasma Prize in 2011. He consults for human and veterinary pharmaceutical companies in New Zealand and Singapore and is an inventor on several international patents.
Aging is associated with drastic optical and biochemical changes in the eye often leading to a decline in visual acuity where vision worsens. Such eye disorders impose a financial burden on the health sector worldwide. Recent estimates of the global cost of sight loss -up to the year 2010- suggest an annual figure of over US$3 trillion (£2.4 trillion). The main disorders leading to sight loss are cataract, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy. Pharmaceutical formulation and drug delivery research has introduced promising eye treatments into the market; nevertheless, there remain unmet clinical needs and limitations associated with performance of conventional eye drops and ointments. Compromised adherence and/or persistence with conventional eye drops that are applied topically to the surface of the eye is primarily related to the need to be applied once, twice (or even up to four times) daily, often as a combination of multiple drugs, to achieve their intended purpose. The intravitreal injection of anti-vascular endothelial growth factor (VEGF) for AMD treatment requires clinical intervention every 4-8 weeks. Therefore, achieving therapeutics drug concentrations at the target site and maintaining such concentration over extended time intervals with minimal undesirable effects, offer renewed opportunities for product research and development, especially when using already approved drugs with well-established safety and efficacy profiles. This talk will review and provide insights withdrawn from our own research on ophthalmic drug delivery systems that are aimed at age-related eye disorders including phase-transition microemulsions, in-situ gels, polymeric and inorganic nanoparticles, personalised ocular inserts and modified contact lenses.
Research Center Pharmaceutical Engineering GmbH, Austria
Time : 11:10-11:50
Sharareh Salar-Behzadi held her diploma in Pharmacy and PhD in Pharmaceutical Technology from University of Vienna. Her experience covers a broad range, including formulation and process development for production of solid dosage forms. She worked on several pharmaceutical manufacturing methods, among them solvent free hot-melt fluid-bed technology, wet fluid-bed granulation, roller compaction and methods for development of nano lipid carriers. She works at Research Center Pharmaceutical Engineering (RCPE) GmbH since 2012 as Project Lead for scientific execution of projects for formulation engineering and development of particulate dosage forms. An important research focus is development of personalized-medicine with advanced stability, based on lipid-based excipients
Statement of the Problem: Lipids and lipid-based excipients are increasingly applied for development of patient-centric products. Their application in the pharmaceutical formulations covers a wide range, from taste-masking of oral dosage forms with modified; both immediate- and extended release profile to development of advanced nanoparticles for pulmonary or parenteral route of drug administration. Despite of this diversity in application, the drug release instability and the lack of mechanistic understanding of it still prevent the larger-scale application of lipidic excipients. This abstract provides a comprehensive overview on the complex solid state behavior of lipids and describes methods for monitoring this behavior for obtaining reliable and reproducible dosage forms.
Methodology & Theoretical Orientation: Solid state behavior of lipids was studied as the response to the composition of formulation and to the critical parameters of the applied product manufacturing process, using X-ray diffraction, PLM and DSC. The applied processes were hot-melt coating for taste-masking and high pressure homogenization for preparation of nanosuspensions. Quality by Design (QbD) tools were used for monitoring the manufacturing process.
Findings: The instability of lipidic formulations can be addressed to both changes in molecular and supra-molecular levels. Changes in molecular level mainly contains polymorphic transformation and alteration in crystallite thickness, which can be monitored by careful selection of formulation composition and process parameters. Certain surfactants can be used as modifier, influencing the kinetic character of polymorphic transition of lipids. Process temperature can be monitored to control both crystallite growth kinetics and polymorphic transition. Understanding the microphase separation of formulations containing emulsifier is necessary and will help to improve the selection of pharmaceutical formulations.
Friedrich-Schiller University, Germany
Time : 11:50-12:30
Dagmar Fischer is a Pharmacist. She has more than 20 years of experience in the field of “Nanocarriers based on synthetic and natural polymers, their formulation and biopharmaceutical characterization”. Furthermore, she has long-standing successful co-operations with many partners in and outside of Europe, in the field of Nano-safety. After completing her PhD in Habilitation at University of Marburg, she joined a biotech company for several years as Head of Preclinical Research and Development. In 2008, she was appointed as a Professor of Pharmaceutical Technology at University Jena.
The natural hydro-polymer bacterial nano cellulose (BNC) is an innovative biomaterial, produced during fermentation by strains of gram-negative bacteria Komagataeibacter xylinus and consisting of about 1% cellulose and 99% water. Although the chemical formula is identical to plant cellulose, the material favors totally different but outstanding material characteristics due to the three-dimensional network of nano-sized fibers. The interest in BNC as drug delivery system dramatically increased during the last years, as the nano-sized 3D-network of BNC is expected to hold a large amount of drug molecules due to its large surface area. However, the highly hydrophilic character limited a broad application especially for the delivery of lipophilic drugs as well as long-term applications. We developed different loading techniques to accomplish a controlled release of drugs from several hours to weeks using BNC produced under lab-scale as well as under high throughput conditions. Native BNC, hybrid systems with different types of the thermo-responsive block-copolymers poloxamers as well as lipid-modified BNC were established. Depending on the type of modification, not only the drug release profile, but also superior material properties such as high compression stability and water binding could be achieved. Using the antiseptic octenidine as model drug, the antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa was not changed by the use of the modified BNC. Excellent biocompatibility of the loaded BNC could be demonstrated after local administration in a shell-less hen’s egg model. In conclusion, controllable short- and long-term delivery systems consisting of poloxamer and lipid modified BNC could be developed as ready-to-use systems e.g. for dermal wound treatment, cosmetics or the use as implants.