Commonly used nonionic surfactants interact differently with the human efflux transporters ABCB1 (p-glycoprotein) and ABCC2 (MRP2)

The efflux transporters ABCB1 (p-glycoprotein) and ABCC2 (MRP2) play an essential role in the limitation of oral bioavailability of drugs. In the last years, pharmaceutical surfactants like cremophor® EL or polysorbate 80 have been shown to interact with ABCB1. However, the knowledge about their influence on ABCC2 is still limited.In this study, the interactions of the nonionic surfactants cremophor® EL, cremophor® RH 40, polysorbate 80, vitamin E TPGS 1000, pluronic® PE 10300 and sucrose ester L-1695 with both efflux transporters were investigated on cellular level.Cell accumulation studies and transport studies were performed using transfected MDCK II cell models. The influence of ABCC2 inhibiting surfactants on the expression level of ABCC2 was also studied.The investigations showed that cremophor® EL, vitamin E TPGS 1000 and higher concentrations of polysorbate 80 inhibit both transporters. Pluronic® PE 10300 and sucrose ester L-1695 inhibit ABCB1 but not ABCC2. Cremophor® RH 40 only shows inhibitory activity on ABCC2. During the investigated incubation period none of the inhibiting surfactants caused an alteration in ABCC2mRNA or protein expression. These findings indicate that the observed interactions are caused by specific inhibition of the transport activity of ABCC2.

Transport of calcein with and without ABCC2 inhibitor probenecid in MDCK-ABCC2 cells.Figure optionsDownload as PowerPoint slide