On Ngoc H, Miller Donald W
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, CANADA.
Curr Pharm Des. 2014;20(10):1499-509. doi: 10.2174/13816128113199990458.
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.
由于血脑屏障（BBB）的限制特性，许多药物向中枢神经系统（CNS）的递送受到限制。构成血脑屏障的脑微血管内皮细胞中细胞旁扩散的减少以及各种药物外排转运蛋白的存在，使得用化疗药物有效治疗脑肿瘤特别困难。虽然P-糖蛋白（P-gp）在限制化疗药物的血脑屏障通透性方面起重要作用，但其他药物外排转运蛋白，如乳腺癌耐药蛋白（BCRP）和多药耐药相关蛋白（MRP），可能会影响脑和脑肿瘤内的化疗水平。本综述探讨了药物外排转运蛋白在化疗药物向脑递送中的限制作用。还讨论了为尽量减少药物外排转运蛋白对血脑屏障的影响以及改善治疗脑肿瘤的化疗反应而采取的不同方法。
