Main description:

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.

Contents:

I. PHYSIOLOGY AND BASIC PRINCIPLES FOR DRUG HANDLING BY THE BRAIN

1. Anatomy and physiology of the blood-brain barriers

N Joan Abbott

2. Recent Progress in Blood-Brain Barrier and Blood-CSF Barrier Transport Research: Pharmaceutical Relevance for Drug Delivery to the Brain

Masanori Tachikawa, Yasuo Uchida, Sumio Ohtsuki and Tetsuya Terasaki

3. Blood-Brain Barrier (BBB) Pharmacoproteomics: A New Research Field Opened up by Quantitative Targeted Absolute Proteomics (QTAP)

Yasuo Uchida, Masanori Tachikawa, Sumio Ohtsuki And Tetsuya Terasaki

4. Drug Metabolism at the Blood-Brain and Blood-CSF Barriers

Xavier Decleves, Nathalie Strazielle, Jean-Michel Scherrmann and Jean-Francois Ghersi-Egea

II. PHARMACOKINETIC CONCEPTS AND METHODS FOR STUDYING DRUG DELIVERY ACROSS THE BLOOD-BRAIN BARRIER

5. Pharmacokinetic Concepts in Brain Drug Delivery

Margareta Hammarlund-Udenaes

6. In vitro models of blood-brain barriers

N Joan Abbott, Diana EM Dolman, Siti R Yusof and Andreas Reichel

7. In situ and in vivo animal models

Quentin Smith and Ramakrishna Samala

8. Principles of PET and its Role in Understanding Drug Delivery to the Brain

Stina Syvanen and Roger N. Gunn

9. PKPD Aspects of Brain Drug Delivery in a Translational Perspective

Elizabeth C.M. de Lange

III. INDUSTRIAL APPROACHES FOR INVESTIGATION OF POTENTIAL CENTRAL NERVOUS SYSTEM DRUGS

10. Drug Discovery Methods for Studying Brain Drug Delivery and Distribution

Irena Loryan and Margareta Hammarlund-Udenaes

11. Prediction of Drug Exposure in the Brain from the Chemical Structure

Markus Friden

12. Integrated Approach to Optimizing CNS Penetration in Drug Discovery: From the old to the new Paradigm and Assessment of Drug-Transporter Interactions

Andreas Reichel

13. Pharmacoeconomic Considerations in CNS Drug Development

David Gray

IV. STRATEGIES FOR IMPROVED CENTRAL NERVOUS SYSTEM DRUG DELIVERY

14. Intranasal Drug Delivery to the Brain

Jeffrey J. Lochhead and Robert G. Thorne

15. Blood-To-Brain Drug Delivery using Nanocarriers

Pieter J. Gaillard, Corine C. Visser, Marco de Boer, Chantal C.M. Appeldoorn and Jaap Rip

16. Development of new Protein Vectors for the Physiologic Delivery of Large Therapeutic Compounds to the CNS

Reinhard Gabathuler

17. CNS Gene Therapy Utilizing Intravenously Administered Viral Vectors

Adam K. Bevan and Brian K. Kaspar

18. Neurosurgical Approaches: Drug Infusion Directly into the Parenchyma or Cerebrospinal Fluid

Krystof Bankiewicz

19. Osmotic Opening of the BBB for Drug Treatment of Brain Tumors (Focus on Methodological Issues)

David Fortin

20. Emerging Engineering Technologies for Opening the BBB

Elisa E. Konofagou

V. BRAIN DRUG DELIVERY IN DISEASE CONDITIONS

21. Disease Influence on BBB Transport in Inflammatory Disorders

Geert Schenk, Gijs Kooij, Arie Reijerkerk and Helga de Vries

22. Disease Influence on BBB Transport in Neurodegenerative Disorders

Elizabeth C.M. de Lange

23. Drug Delivery in the Context of Stroke and Brain Trauma

Richard F. Keep, Jianming Xiang, Ningna Zhou and Anuska V. Andjelkovic

24. Which Drug or Drug Delivery Method can change Clinical Practice for Brain Tumor Therapy?

Tali Siegal

Appending - Primer on Central Nervous System Structure / Function and the Vasculature, Ventricular System and Fluids of the Brain. Robert Thorne