Su Yaming, Sinko Patrick J
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Expert Opin Drug Deliv. 2006 May;3(3):419-35. doi: 10.1517/17425247.3.3.419.
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.
作用于中枢神经系统（CNS）的药物研发因难以透过血脑屏障（BBB）而受到显著阻碍。本文旨在为读者提供一个关于需要进入大脑以引发药理活性的药物发现与研发中重要问题的批判性综述，特别关注以下几点：i）药物转运体在脑渗透中的作用以及如何操控它们以提高药物的脑生物利用度；ii）用于测量药物跨血脑屏障转运的常用体外和体内方法的成功应用、局限性和挑战；iii）对最近开发的促进药物进入大脑的策略（例如，通过化学抑制剂调节外排转运体以及利用血脑屏障处的天然转运系统的递送载体）的讨论。
