Transport mechanisms of mmePEG750P(CL-co-TMC) polymeric micelles across the intestinal barrier

Monomethylether poly(ethyleneglycol)7(50)-Poly(caprolactone-co-trimethylene carbonate) (mnnePEG(750)P(CL-co-TMC) which spontaneously form micelles, can cross lipid bilayers via passive diffusion and demonstrate an oral bioavailability of 40% in rats. The aim of the current work was to study the transport mechanism(s) of drug-loaded mmePEG(750)P(CL-co-TMC) micelles across the intestinal barrier. The transport of radiolabelled polymer across Caco-2 cell monolayer was investigated by disrupting tight junctions and by inhibiting endocytosis. The polymer and drugs loaded in micelles independently crossed Caco-2 cell monolayers and did not use either the paracellular route or M-cells. The polymer did not affect P-gp pumps. This mechanistic study suggests that whereas drug-loaded micelles were absorbed by fluid-phase endocytosis, polymeric unimers diffused passively across the membrane concomitantly with micellar endocytosis. (c) 2007 Elsevier B.V. All rights reserved.