Transporter-Based Delivery of Anticancer Drugs to the Brain: Improving Brain Penetration by Minimizing Drug Efflux at the Blood-Brain Barrier

ISSN: 1873-4286 (Online)
ISSN: 1381-6128 (Print)


Volume 20, 42 Issues, 2014


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Transporter-Based Delivery of Anticancer Drugs to the Brain: Improving Brain Penetration by Minimizing Drug Efflux at the Blood-Brain Barrier

Author(s): Ngoc H. On and Donald W. Miller

Affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, CANADA.

Abstract

The delivery of many drugs to the central nervous system (CNS) is limited due to the restrictive nature of the blood-brain barrier (BBB). The reduced paracellular diffusion and the presence of various drug efflux transporters in the brain microvessel endothelial cells forming the BBB make effective treatment of brain tumors with chemotherapeutic agents particularly problematic. While Pglycoprotein (P-gp) plays an important role in limiting BBB permeability of chemotherapeutic agents, other drug efflux transporters such as breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs) are likely to impact on chemotherapeutic levels within the brain and brain tumor. The current review examines the restrictive role that drug efflux transporters have in the delivery of chemotherapeutic agents to the brain. Consideration of different approaches taken to minimize the impact of drug efflux transporters in the BBB and improve chemotherapeutic response in treating brain tumors is also discussed.

Keywords: Blood brain barrier (BBB), brain tumor, permeability, drug efflux transport, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), chemotherapeutic agents.

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Article Details

Volume: 20
Issue Number: 10
First Page: 1499
Last Page: 1509
Page Count: 11
DOI: 10.2174/13816128113199990458
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