Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, ROC.
Colloids Surf B Biointerfaces. 2012 Mar 1;91:291-5. doi: 10.1016/j.colsurfb.2011.11.020. Epub 2011 Nov 20.
An exposure to an electromagnetic field (EMF) has been shown to enhance the membrane permeability of endothelial cells. This study investigates the effect of EMF on the modulation of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) for delivering saquinavir (SQV) and azidothymidine (AZT). To assess the transport of SQV and AZT, an EMF and P-gp/MRP (transport protein) inhibitors were employed to stimulate confluent human brain-microvascular endothelial cells (HBMECs) with the regulation of human astrocytes. SQV at 40 μM and AZT at 300 μM were acceptable dosages for the viability of HBMECs. Under an EMF, verapamil showed a higher ability to elevate the permeation across the blood-brain barrier (BBB) than probenecid during treating with SQV. The reverse was true during treating with AZT. After an exposure to an EMF and administration of SQV and AZT, P-gp and MRP1 localized on the luminal side of HBMECs, exhibiting polar characteristics of the cell membranes. The synergetic effect of an EMF exposure and efflux protein inhibition can be promising in delivering antiretroviral drugs across the BBB.
电磁场（EMF）暴露已被证明可增强内皮细胞的膜通透性。本研究探讨了 EMF 对 P-糖蛋白（P-gp）和多药耐药相关蛋白（MRP）调节的影响，以输送沙奎那韦（SQV）和叠氮胸苷（AZT）。为了评估 SQV 和 AZT 的转运，使用 EMF 和 P-gp/MRP（转运蛋白）抑制剂刺激具有人星形胶质细胞调节的人脑微血管内皮细胞（HBMEC）的汇合。对于 HBMEC 的活力，40 μM 的 SQV 和 300 μM 的 AZT 是可接受的剂量。在 EMF 下，维拉帕米在处理 SQV 时比丙磺舒更能提高穿过血脑屏障（BBB）的渗透能力。在处理 AZT 时则相反。在暴露于 EMF 并给予 SQV 和 AZT 后，P-gp 和 MRP1 定位于 HBMEC 的腔侧，表现出细胞膜的极性特征。EMF 暴露和外排蛋白抑制的协同作用有望在将抗逆转录病毒药物递送至 BBB 中发挥作用。
