期刊
EXPERT OPINION ON DRUG DELIVERY
卷 3, 期 3, 页码 419-435出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/17425247.3.3.419
关键词
blood-brain barrier; brain capillary endothelial cells; Caco-2 cell; cell penetrating peptides; efflux; Madin-Darby canine kidney cell; P-glycoprotein; P-glycoprotein inhibitor; pegylated immunoliposome; receptor-mediated transport; transporter
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.
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