Pluronic P85 increases permeability of a broad spectrum of drugs in polarized BBMEC and Caco-2 cell monolayers

Purpose. Previous studies demonstrated that inhibition of P glycoprotein (P -gp) by Pluronic P85 (P85) block copolymer increases apical (AP) to basolat eral (BL) transport of rhodamine 123 (R123) in the polarized monolayers of bovine brain microvessel endothelial cells (BBMEC) and Caco-2 cells. The pr esent work examines the effects of P85 on the transport of fluorescein (Flu ), doxorubicin (Dox), etoposide (Et), taxol (Tax), 3'-azido-3'-deoxythymidi ne (AZT), valproic acid (VPA) and loperamide (Lo) using BBMEC and Caco-2 mo nolayers as in vitro models of the blood brain barrier and intestinal epith elium respectively. Methods. Drug permeability studies were performed on the confluent BBMEC an d Caco-2 cell monolayers mounted in Side-Bi-Side diffusion cells. Results. Exposure of the cells to P85 significantly enhanced AP to BL perme ability coefficients of Flu, Tax, Dox and AZT in both cell models. Further, P85 enhanced AP to BL transport of Et, VPA and Lo in Caco-2 monolayers. No changes in the permeability coefficients of the paracellular marker mannit ol were observed in the presence of the copolymer. Conclusions. P85 increases AP to BL permeability in BBMEC and Caco-2 monola yers with respect to a broad panel of structurally diverse compounds, that were previously shown to be affected by P-gp and/ or multidrug resistance a ssociated protein (MRP) efflux systems. Broad specificity of the block copo lymer effects with respect to drugs and efflux systems appears to be a valu able property in view of developing pharmaceutical formulations to increase drug accumulation in selected organs and overcome both acquired and intrin sic drug resistance that limits the effectiveness of many chemotherapeutic agents.