Pathways For Drug Delivery To The Central Nervous System

1 2 Yan Zhang and Donald W. Miller

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-6025

3.1. Introduction

3.1.1. Importance of drug delivery to the central nervous system (CNS)

3.1.2. Cellular barriers to drug delivery in the CNS

3.1.3. General approaches for increasing brain penetration of drugs

3.2. Direct administration of drugs into the brain

3.2.1. Intracerebral administration

3.2.2. Intrathecal administration

3.2.3. Nasal administration

3.3. BBB disruption

3.3.1. Osmotic agents

3.3.2. Bradykinin analogs

3.3.3. Alkylglycerols

3.4. Transcellular delivery routes in the BBB

3.4.1. Passive diffusion

3.4.2. Inwardly directed transport systems in the BBB

3.4.2.1. Amino acid transporters

3.4.2.2. Glucose transporters

3.4.2.3. Monocarboxylic acid transporter

3.4.2.4. Nucleoside transporters

'Current address, Pfizer Global Research and Development, PDM Department, Building 20, Room 332 E, 2800 Plymouth Road, Ann Arbor, MI 48105 2Corresponding author

Drug Delivery: Principles and Applications Edited by Binghe Wang, Teruna Siahaan, and Richard Soltero

ISBN 0-471-47489-4 © 2005 John Wiley & Sons, Inc.

3.4.2.5. Peptide transport systems

3.4.2.6. Considerations for carrier-mediated transport in the CNS

3.4.3. Vesicular transport in the BBB

3.4.3.1. Transferrin receptor-mediated vesicular transport

3.4.3.2. Insulin receptor-mediated vesicular transport

3.4.4. Drug efflux transporter systems in the BBB

3.4.4.2. Multidrug resistance-associated protein (MRP)

3.4.4.3. Breast cancer resistance protein (BCRP)

3.4.4.4. Modulation of drug efflux activity to increase CNS drug delivery

3.5. Summary References

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