Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis

This book elaborates on drug delivery targeting via intracellular delivery, specifically through the Receptor Mediated Endocytosis (RME) approach, due to the involvement of cellular receptors in various grave diseases. Targeted delivery relies on two basic approaches, passive and active targeting. While passive targeting approaches have shown great promise, the improved selectivity achieved with active targeting approaches has resulted in significantly higher efficacy. Interestingly there are numerous strategies for active targeting, many of which are already highlighted in, Targeted Drug Delivery: Concepts and Applications. Nevertheless an exciting and practical strategy for active targeting, which could enable high intracellular delivery, is through exploitation of RME. Cells in the body express receptors to enable various physiological and biochemical processes. As a result, many of these receptors are overexpressed in pathological conditions, or newer receptors expressed due to defective cellular functioning. RME is based on exploitation of such receptors to achieve intracellular delivery. While targeted delivery can have manifold applications, in this book we focus on two major and challenging therapeutic areas; i) Cancer and ii) Infectious Diseases. Targeted Intracellular Drug Delivery by Receptor Medicated Endocytosis discusses the major receptors that are useful for targeted delivery for these afflictions. A major section of this book is dedicated to details regarding their occurrence and location, the recognition domain of the receptor, structure activity relationship of substrate /ligand for selective binding, ligands explored, antagonists for ligand binding and relevance of these aspects for therapy of cancer and infectious diseases. These facets are elucidated with the help of specific examples from academic research and also emphasize commercial products, wherever relevant. In vitro cellular models relied onfor assessing receptor mediated cellular targeting and in vivo models depicting clinical efficacy are focused on in a separate section. Finally, we briefly discuss the regulatory and toxicity issues that may be associated specifically with the RME approach of intracellular drug delivery.

Padma V. Devarajan, PhD (Tech), is Professor in Pharmacy and former Head, Department of Pharmaceutical Sciences and Technology at the Institute of Chemical Technology (ICT), Mumbai, India. Her research interests include nano carriers for targeted delivery in cancer and infectious diseases, innovative approaches in scale-up of nano drug delivery systems (DDS), bioenhancement strategies, and mucosal DDS as alternatives to parenteral administration for protein and nucleic acid delivery. She is editor of Targeted Drug Delivery-Concepts and Design, published by Springer, author of several book chapters and has publications in peer reviewed high impact journals. She is a member on the Editorial board of European Journal of Drug Metabolism and Pharmacokinetics and the Asian Journal of Pharmaceutical Sciences and peer reviewer for a number of International Journals. She has served as Board Member, Member on the Board of Scientific Advisors, Chair of the Young Scientist MentorProtégé Sub-committee of the Controlled Release Society Inc., USA and Chair- Outstanding Paper Award Committee, Drug Development and Translational research. Prof. Devarajan is a nominated Fellow of the Maharashtra Academy of Sciences, India, and recipient of number of awards including the American Association of Indian Pharmaceutical Scientists (AAiPS) Distinguished Educator and Researcher Award, and Innovation Awards for pioneering research in Nanotechnology and Targeted Drug Delivery Systems. Prajakta Dandekar received her PhD from the Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai. Her doctoral research involved the development of polymeric nanoparticles for natural therapeutic agents. Later, she joined the Department of Macromolecular Organic Chemistry, University of Saarland, Saarbrucken, as a post-doctoral researcher and was involved in formulating nanoparticles of new hydrophobic starch polymers for encapsulating hydrophobic anti-cancer actives. She was the first woman scientist from India to be awarded the European Respiratory Society-Marie Curie Joint Postdoctoral Fellowship (long-term) and conducted the associated research involving formulation of nanoparticles for intracellular siRNA delivery at the Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrucken, Germany. From January 2012 until October 2014, she worked as Dr. John Kapoor Assistant Professorin Pharmaceutical Technology at the Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai. Currently, she is UGC Assistant Professor in Engineering Sciences, in the same department. Her research interests involve design of siRNA-polymer nanocarriers, development of in vitro 2D and 3D cellular models, and developing biopolymer-scaffolds and microfluidic devices for tissue engineering. Anisha A. D'Souza is currently working as Research Formulation Scientist at Piramal Enterprises Limited, Mumbai. She received her PhD (Tech.) in Pharmaceutics from the Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai (ICT, Formerly known as UDCT). She was the recipient of the most coveted and prestigious 'Prof. M. M. Sharma Doctoral Fellowship' at ICT. Subsequently, during her post-doctoral tenure at IIT-Bombay, she has worked on delivery of micronutrients encapsulated nanoparticles incorporated in different cosmetics for improving mother and child health. Her research interest encompasses colloidal drug delivery systems viz., polymeric and solid lipid nanoparticles for enhanced bioavailability, controlled delivery and targeting. She has published research papers and reviews in peer reviewed journals and has coauthored number of book chapters.