1: J Control Release. 2007 Dec 20;124(3):134-43. Epub 2007 Sep 7.

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

Mathot F, des Rieux A, Ariën A, Schneider YJ, Brewster M, Préat V.

Université catholique de Louvain, Unité de Pharmacie Galénique, Avenue E. Mounier
73.20, UCL, 1200 Brussels, Belgium.

Monomethylether poly(ethyleneglycol)(750)-poly(caprolactone-co-trimethylene
carbonate) (mmePEG750)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 mmePEG750P(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.

PMID: 17928087 [PubMed - in process]

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