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.

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.

The availability of various in vitro and in vivo techniques has considerably advanced the research on drug transport and metabolism across the blood-brain barrier (BBB). These specialized and sophisticated experimental strategies are of fundamental importance if one is to gain a greater understanding of enhanced and selective drug delivery to the brain. The reader will find in this book methods for in vitro endothelial/astrocyte cell culture models, and for in vivo intracerebral microdialysis to study drug tranport across the BBB. This book, however, is not merely a laboratory manual consisting of recipes for BBB research; it permits the presentation of the different methods in fine detail, revealing tricks and short cuts that frequently do not appear in the literature. The researcher is well aware that differences (subtle or otherwise) in experimental steps used in different laboratories may influence the outcome of any particular procedure. The book also illustrates the accessibility and the application of the different methods in different species. Background information of the protocol is given in every chapter, which also contains a literature list that the reader may wish to refer to for further information. This volume will be invaluable to basic researchers as well as to those involved in the search for agents suitable for pharmaceutic intervention in the central nervous system.

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, and drug industry perspectives. 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. ​

Written and edited by the world's foremost authorities, the Second Edition of this landmark work is a current, comprehensive reference on cerebral blood flow and metabolism. The book covers the entire field in a systematic and coherent way and synthesizes the diverse body of basic science and clinical literature. The reader will gain a complete understanding of the anatomical, physiological, and pharmacological bases of the cerebral circulation, its regulation in health and disease, and the pathophysiological disturbances occurring in cerebrovascular disorders. Coverage includes stimulating discussions of future directions for research and therapeutic intervention.

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.