Modulation of efflux proteins by electromagnetic field for delivering azidothymidine and saquinavir into the brain

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.

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► SQV at 40 μM and AZT at 300 μM are acceptable dosages for the viability of endothelia.
► Probenecid showed a higher BBB permeation than verapamil during treatment with SQV and AZT.
► P-gp and MRP1 localized on the luminal side of endothelia after an electromagnetic field exposure.
► Electromagnetic field and efflux protein inhibitors induce synergetic effect on BBB penetration.