Drug delivery across the blood–brain barrier: why is it difficult? how to measure and improve it?
- 26 April 2006
- journal article
- review article
- Published by Informa Healthcare in Expert Opinion on Drug Delivery
- Vol. 3 (3), 419-435
- https://doi.org/10.1517/17425247.3.3.419
Abstract
The development of drugs that act in the CNS has been significantly impeded by the difficulty of delivering them across the blood-brain barrier (BBB). This article aims to provide the reader with a critical overview of important issues in the discovery and development of drugs that need to enter the brain to elicit pharmacological activity, focusing particularly on i) the role of drug transporters in brain permeation and how to manipulate them to enhance drug brain bioavailability; ii) the successful application, limitations and challenges of commonly used in vitro and in vivo methodologies for measuring drug transport across the BBB, and iii) a discussion of recently developed strategies (e.g., modulation of efflux transporters by chemical inhibitors and the employment of delivery vectors taking advantage of native transport systems at the BBB) for facilitating drug penetration into the brain.Keywords
This publication has 99 references indexed in Scilit:
- Delivery of β-Galactosidase to Mouse Brain via the Blood-Brain Barrier Transferrin ReceptorJournal of Pharmacology and Experimental Therapeutics, 2005
- Improved penetration of docetaxel into the brain by co-administration of inhibitors of P-glycoproteinEuropean Journal Of Cancer, 2004
- Endothelial-pericyte interactions in angiogenesisCell and tissue research, 2003
- Vascular Proteomics and Subtractive Antibody Expression CloningMolecular & Cellular Proteomics, 2002
- Development of anIn SituMouse Brain Perfusion Model and its Application tomdr1aP-Glycoprotein-Deficient MiceJournal of Cerebral Blood Flow & Metabolism, 2000
- Molecular Cloning and Characterization of Two Novel Human Renal Organic Anion Transporters (hOAT1 and hOAT3)Biochemical and Biophysical Research Communications, 1999
- Brain Microvascular and Astrocyte Localization of P‐GlycoproteinJournal of Neurochemistry, 1997
- Astroglial cells inhibit the increasing permeability of brain endothelial cell monolayer following hypoxia/reoxygenationNeuroscience Letters, 1996
- Glucose transporter localization in brain using light and electron immunocytochemistryJournal of Neuroscience Research, 1989
- Electrical resistance of brain microvascular endotheliumBrain Research, 1982