The Blood Brain Barrier And Drug Delivery To The Cns

This timely and compact monograph addresses how to determine drug permeability across the blood-brain barrier more effectively. Focusing on the physiological mechanisms that influence the passage of agents into the brain, the book covers the latest research on the blood-brain barrier, the current problems of and solutions to drug delivery to the central nervous system (CNS), existing strategies, and prospects for future research. Avoid excessive in vivo experimentation and utilize timesaving in vitro techniques. A concise reference with reviews from nearly 40 international specialists in diverse fields, The Blood-Brain Barrier and Drug Delivery to the CNS assesses the properties of the blood-brain barrier to determine and measure drug permeability in animals and humans presents techniques to predict successful drug uptake through in vitro systems or by computation of physicochemical parameters examines the multidrug resistance protein P-glycoprotein as a natural transporter analyzes current drug designs to known requirements for transport looks at drug delivery systems for the brain and much more! Densely packed with over 800 literature references, drawings, photographs, x-rays, tables, and equations, The Blood-Brain Barrier and Drug Delivery to the CNS is a vital addition to the bookshelves of biochemists, pharmacists, clinical and research pharmacologists, neuroscientists and neurologists, and graduate and medical school students in these disciplines.

This timely and compact monograph addresses how to determine drug permeability across the blood-brain barrier more effectively. Focusing on the physiological mechanisms that influence the passage of agents into the brain, the book covers the latest research on the blood-brain barrier, the current problems of and solutions to drug delivery to the central nervous system (CNS), existing strategies, and prospects for future research.Avoid excessive in vivo experimentation and utilize timesaving in vitro techniques. A concise reference with reviews from nearly 40 international specialists in diverse fields, The Blood-Brain Barrier and Drug Delivery to the CNSassesses the properties of the blood-brain barrier to determine and measure drug permeability in animals and humans presents techniques to predict successful drug uptake through in vitro systems or by computation of physicochemical parameters examines the multidrug resistance protein P-glycoprotein as a natural transporter analyzes current drug designs to known requirements for transport looks at drug delivery systems for the brain and much more!Densely packed with over 800 literature references, drawings, photographs, x-rays, tables, and equations, The Blood-Brain Barrier and Drug Delivery to the CNS is a vital addition to the bookshelves of biochemists, pharmacists, clinical and research pharmacologists, neuroscientists and neurologists, and graduate and medical school students in these disciplines.

Focused on central nervous system (CNS) drug discovery efforts, this book educates drug researchers about the blood-brain barrier (BBB) so they can affect important improvements in one of the most significant – and most challenging – areas of drug discovery. • Written by world experts to provide practical solutions to increase brain penetration or minimize CNS side-effects • Reviews state-of-the-art in silico, in vitro, and in vivo tools to assess brain penetration and advanced CNS drug delivery strategies • Covers BBB physiology, medicinal chemistry design principles, free drug hypothesis for the BBB, and transport mechanisms including passive diffusion, uptake/efflux transporters, and receptor-mediated processes • Highlights the advances in modelling BBB pharmacokinetics and dynamics relationships (PK/PD) and physiologically-based pharmacokinetics (PBPK) • Discusses case studies of successful CNS and non-CNS drugs, lessons learned and paths to the market

The development of new CNS drugs is notoriously difficult. Drugs must reach CNS target sites for action and these sites are protected by a number of barriers, the most important being the blood–brain barrier (BBB). Many factors are therefore critical to consider for CNS drug delivery, e.g. active/passive transport across the BBB, intra-brain distribution, and central/systemic pharmacokinetics, to name a few. Neurological disease and trauma conditions add further complexity because CNS barriers, drug distribution and pharmacokinetics are dynamic and often changed by disease/trauma. Knowledge of all these factors and their interplay in different conditions is of utmost importance for proper CNS drug development and disease treatment. In recent years much information has become available for a better understanding of the many factors important for CNS drug delivery and how they interact to affect drug action. This book describes small and large drug delivery to the brain with an emphasis on the physiology of the BBB and the principles and concepts for drug delivery across the BBB and distribution within the brain. It contains methods descriptions for studying drug delivery, routes and approaches of administering drugs into the brain, the influence of disease, drug industry perspectives, and a primer on neuroanatomy and physiological considerations written specifically for drug delivery scientists. Therewith, it contributes to an in-depth understanding of the interplay between brain (patho)-physiology and drug characteristics. Furthermore, the content is designed to be both cutting-edge and educational, so that the book can be used in high-level training of academic and industry scientists with full references to original publications.

The vasculature of the central nervous system (eNS) is characterized by the existence of the blood-brain barrier (BBB), which can be regarded as both an anatomical and physiological phenomenon. The BBB is formed by a complex cellular system of endothelial cells, astroglia, pericytes, perivascular macrophages and a basal membrane, although the anatomic substrate of the BBB is the interendothelial tight junctions that form a continuous sealing. The BBB serves as an exquisitely controlled, functional gate to the eNS. It not only protects the brain from agents in the blood that could impair neurological function, but also controls the influx and efflux of numerous substances to maintain proper homeostasis and provide the brain with necessary nutrients. The structural and functional integrity of the BBB was shown to be dramatically altered during various diseases of the eNS, including neoplasia, ischemia, trauma, hypertension, inflammation and epilepsy. Recent years research has partially elucidated the mechanisms underlying the development of some of these brain disorders as well as the pathways used by different pathogens, like bacteria and viruses, to initiate eNS infections. The development of in vitro models of the BBB had instrumental role in the understanding of the involvement of the BBB in the pathogenesis of several eNS diseases. The intimate, functional association between the function of the brain and the activity of the BBB makes the later a target for pharmacological modulation that will expand the therapeutic possibilities for a range of neurological diseases.

Playing an important role in the treatment of neurological disorders, the delivery of drugs to central nervous system (CNS), both administered directly and administered systematically for targeted action, encounters a major challenge in the form of the blood-brain barrier (BBB), which limits the access of drugs to the brain substance. In Drug Delivery to the Central Nervous System, experts in the field present essential methods used to deliver therapeutics across the BBB, both in experimental animals and in humans. In addition to those methods, several overviews of innovative methods and their applications are presented in order to give a glimpse of the future of this research. As a volume in the successful Neuromethods series, this book presents its protocols with the kind of detailed description and implementation advice that is crucial for getting optimal results. Authoritative and cutting-edge, Drug Delivery to the Central Nervous System serves as an ideal guide to scientists continuing to pursue knowledge of the delicate interactions between pharmaceuticals and the brain.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

Nanotechnology Methods for Neurological Diseases and Brain Tumors: Drug Delivery across the Blood-Brain Barrier compiles the latest (and future potential) treatment strategies for brain tumors and neurological diseases, in particular Alzheimer’s, Parkinson’s and stroke, those that bypass the blood/brain barrier. The current understanding of brain drug delivery and access is discussed in Chapter One, with the next section focusing on the implementation of the nose-to-brain intranasal route in brain-targeted drug delivery. In addition, nanotechnology-based brain drug delivery is covered in Chapter Three. This avenue offers impressive improvement in the treatment of neurological diseases and brain tumors by using bio-engineered systems that interact with biological systems at a molecular level. In Chapter Four, emphasis is placed on the need for brain-targeted experimental models that mimic disease conditions. Final chapters discuss the very latest advances in targeted treatment strategies for neurological diseases and brain tumors. Comprehensive guide for up-to-date views on the latest advances in targeted treatment strategies for brain tumors and neurological diseases Designed with a multidisciplinary approach that links neurology, neuro-oncology and nanoscience to drug delivery to the brain with an emphasis on the blood-brain-barrier Written in a language that makes it easy to understand nanotechnology drug delivery techniques Presents a unique book that also covers advanced treatment approaches of neurological diseases and brain tumors