EFFECTS OF PLURONIC P85 UNIMERS AND MICELLES ON DRUG PERMEABILITY IN POLARIZED BBMEC AND CACO-2 CELLS

Purpose, Using polarized bovine brain microvessel endothelial cells (B BMEC) monolayers as in vitro model of the blood brain barrier and Caco -2 monolayers as a model of the intestinal epithelium, the present wor k investigates the effects of Pluronic P85 block copolymer (P85) on th e transport of the P-gycoprotein (P-gp)- dependent probe, rhodamine 12 3 (R123). Methods. The permeability and cell efflux studies are perfor med with the confluent cell monolayers using Side-Bi-Side diffusion ce lls. Results. At concentrations below the critical micelle concentrati on, P85 inhibits P-gp efflux systems of the BBMEC and Caco-2 cell mono layers resulting in an increase in the apical to basolateral permeabil ity of R123. In contrast, at high concentrations of P85 the drug incor porates into the micelles, enters the cells and is then recycled back out to the apical side resulting in decrease in R123 transport across the cell monolayers. Apical to basolateral permeability of micelle-inc orporated R123 in BBMEC monolayers was increased by prior conjugation of P85 with insulin, suggesting that modified micelles undergo recepto r-mediated transcytosis. Conclusions. Pluronic block copolymers can in crease membrane transport and transcellular permeability in brain micr ovessel endothelial cells and intestinal epithelium cells. This sugges ts that these block copolymers may be useful in designing formulations to increase brain and oral absorption of select drugs.