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Current Drug Delivery


ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Drug Delivery Across the Blood-Brain Barrier

Author(s): Y. Chen, G. Dalwadi and H. A.E. Benson

Volume 1, Issue 4, 2004

Page: [361 - 376] Pages: 16

DOI: 10.2174/1567201043334542

Price: $65


The brain is protected and isolated from the general circulation by a highly efficient blood-brain barrier. This is characterised by relatively impermeable endothelial cells with tight junctions, enzymatic activity and active efflux transport systems. Consequently the blood-brain barrier is designed to permit selective transport of molecules that are essential for brain function. This creates a considerable challenge for the treatment of central nervous system diseases requiring therapeutic levels of drug to enter the brain. Some small lipophilic drugs diffuse across the blood-brain barriersufficiently well to be efficacious. However, many potentially useful drugs are excluded. This review provides an insight into the current research into technologies to target small molecules, peptides and proteins to the brain. A brief review of the nature of the blood-brain barrier and its transport mechanisms is provided. Strategies to target and improve transport across the blood-brain barrier include the prodrug-lipidisation approach, sequential metabolism chemical delivery systems, drug-vectors, liposomes and nanoparticles. Included is the discussion of techniques to minimise clearance from the circulation by the reticuloendothelial system in order to extend circulation residence time and optimise the opportunity for interaction between the drug delivery system and the blood-brain barrier.

Keywords: brain, blood-brain barrier, drug targeting, nanoparticle, liposome, drug-vector

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