Drug Delivery to the Brain : Physiological Concepts, Methodologies and Approaches / [E-Book]

Part I-Physiology and Basic Principles of Drug Handling for the CNS -- Anatomy and Physiology of the Blood Brain Barriers -- Drug Delivery to the Brain: Integrating Neuroscience, Physiology, and Brain Barriers Science -- Brain Delivery of Therapeutics via Transcytosis: Types and Mechanisms of Vesicle-Mediated Transport Across the BBB -- Brain- Arachnoid Barrier as an Important Clearance Pathway from CSF -- BBB Pharmacoproteomics: Quantitative Targeted Absolute Proteomics (QTAP): Species Differences -- Drug Metabolism at the BBB and the BCFSB -- PART II-PK Concepts and Methods for Studying CNS Drug Delivery -- Pharmacokinetics Concepts in Brain Drug Delivery -- In Vitro Models of CNS Barriers -- Human In Vitro BBB Models Derived from Pluripotent Stem Cells -- In situ and In vivo Animal Models -- Principles of PET and Its Role in Understanding Drug Delivery to the Brain -- Prediction of CNS PK and PD Using Translational Research Approaches -- Part III-Industrial Approachesfor Investigation of Potential CNS Drugs -- Drug Discovery Methods for Studying Brain Drug Delivery and Distribution -- Prediction of Drug Exposure in the Brain From the Chemical Structure -- Integrated Approach to Optimizing CNS Penetration in Drug Discovery -- Part IV: Strategies for Improved CNS Drug Delivery -- Intranasal Drug Delivery to the Brain -- Blood to Brain Drug Delivery Using Nanocarriers -- Enhancing CNS Exposure Through Brain Endothelial Cell RMT-Exploiting the Transferrin Receptor at the BBB -- Therapeutic Osmotic Modification of the BBB in the Treatment of CNS Pathologies -- Biophysical Perspectives on BBB Permeability Enhancement by Ultrasound and Microbubbles for Targeted Drug Delivery in the Clinical Setting -- Optimization of Blood Brain Barrier Opening With Focused Ultrasound-The Animal Perspective -- CNS Gene Therapy Using Adeno-Associated Virus (AAV) Vectors -- Part V-CNS Drug Delivery in Disease Conditions -- Disease Influence on BBB Transport in Neurodegeneration and Neuroinflammation -- Enhancing Drug Delivery in the Setting of Stroke and Brain Injury -- Drug Delivery to tumor Metastases in the Brain-(Including PK PD Free Fraction Active Conc.) -- Drug Delivery to Primary Tumors in the Brain-(Including PK PD Free Fraction Active Conc.) -- Appendix:CNS Anatomy, Function, Vasculature and Fluid Exchange: Primer for Drug Delivery Scientists.

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 anemphasis 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. .