Tsuji A, Tamai I
Department of Pharmacobio-Dynamics, Faculty of Pharmaceutical Sciences Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Adv Drug Deliv Rev. 1999 Apr 5;36(2-3):277-290. doi: 10.1016/s0169-409x(98)00084-2.
In the drug development process, it remains a difficult task to regulate the entry of the drugs. However, recent progress in studies of the transporter-mediated influx and efflux of endogenous and exogenous compounds, including synthetic drugs, across the blood-brain barrier (BBB) is beginning to provide a rational basis for controlling drug distribution to the brain. This paper describes mechanisms established in the last decade for carrier-mediated influx and efflux of drugs and endocytosis of biologically active peptides across the BBB. The transport systems at the BBB described here are the uptake transporters for nutrients, such as amino acids and hexoses, monocarboxylates, amines, carnitine and glutathione and efflux transporters, such as P-glycoprotein and multiple organic anion transporters. Delivery of cationized peptides across the BBB via adsorptive-mediated endocytosis is also described. By utilizing such highly specific transport mechanisms, it should be possible to establish strategies to regulate the entry of candidate drugs, including peptides, into the brain.
在药物研发过程中，调控药物进入体内仍然是一项艰巨的任务。然而，近年来在转运体介导内源性和外源性化合物（包括合成药物）跨血脑屏障（BBB）的流入和流出方面的研究进展，开始为控制药物在脑内的分布提供合理依据。本文描述了过去十年中建立的载体介导药物跨血脑屏障流入和流出以及生物活性肽内吞作用的机制。这里描述的血脑屏障转运系统包括营养物质（如氨基酸、己糖、单羧酸、胺、肉碱和谷胱甘肽）的摄取转运体以及外排转运体（如P-糖蛋白和多种有机阴离子转运体）。还介绍了通过吸附介导的内吞作用使阳离子化肽跨血脑屏障的递送。通过利用这种高度特异性的转运机制，应该有可能制定策略来调控包括肽在内的候选药物进入脑内。
