Modulation of drug efflux transporters induced by low intensity focused ultrasound.

The blood-brain barrier (BBB) provides an obstacle to the entry of drugs into the brain. BBB is mainly constituted of endothelial cells connected by tight junctions (TJs). The TJs together with efflux pumps as the P-glycoprotein (Pgp) and the breast cancer resistance protein (BCRP) limit molecules to pass from the blood to the brain. Focused ultrasound (FUS) with microbubbles can reversibly detach TJs. However, very little is known about the effect of FUS on the expression of efflux transporters. We investigated the effects of FUS on Pgp/BRCP expressions up to 2 weeks after sonication. BBB was disrupted in 12 wild-type rats. BCRP and Pgp expressions were imaged by immunohistochemistry at 1, 3, 7 and 14 days after FUS. Our results indicate that FUS-induced BBB opening is capable of i) decreasing P-gp expression up to 3 days after sonication in both the treated and in the contralateral brain regions and is capable of ii) overexpressing BCRP up to 7 days after FUS in the sonicated regions only. Our findings may help improve FUS-aided drug delivery strategies by considering both the mechanical effect on the TJs and the regulation of P-gp and BCRP.