Tsuji A
Department of Pharmacobio-Dynamics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Ther Drug Monit. 1998 Oct;20(5):588-90. doi: 10.1097/00007691-199810000-00024.
Several lipophilic, cytotoxic drugs, or both, (including anticancer drugs [Vinca alkaloids, doxorubicin, cyclosporin A, and digoxin]) have proven to be actively effluxed by P-glycoprotein (P-gp) expressed at the luminal membrane of the brain capillary endothelial cells, resulting in the very low apparent blood-brain barrier (BBB) permeation of these P-gp substrates from the blood circulating to the brain. In rats inoculated with 9L-glioma cells into the brain, the endothelial cells of tumor-associated vessels allowed easy penetration of anticancer drugs (ranimustine and doxorubicin) in tumor regions, although the normal BBB function still operated at the normal brain region to provide a barrier to the accumulation of P-gp substrates. A detailed knowledge of the BBB function would be very helpful in developing improved delivery systems of anticancer drugs to brain tumors.
几种亲脂性、细胞毒性药物或两者兼具（包括抗癌药物[长春花生物碱、阿霉素、环孢菌素A和地高辛]）已被证实可被脑毛细血管内皮细胞腔膜上表达的P-糖蛋白（P-gp）主动外排，导致这些P-gp底物从血液循环到脑时血脑屏障（BBB）的表观渗透率极低。在向脑内接种9L胶质瘤细胞的大鼠中，肿瘤相关血管的内皮细胞使抗癌药物（雷莫司汀和阿霉素）易于渗透到肿瘤区域，尽管正常的BBB功能在正常脑区仍发挥作用，为P-gp底物的蓄积提供屏障。深入了解BBB功能对于开发改进的抗癌药物向脑肿瘤的递送系统非常有帮助。
