Transport mechanisms of mmePEG750P(CL-co-TMC) polymeric micelles across the intestinal barrier.
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.
Mathot
Frédéric
F
Université catholique de Louvain, Unité de Pharmacie Galénique, Avenue E. Mounier 73.20, UCL, 1200 Brussels, Belgium.
des Rieux
A
A
Ariën
A
A
Schneider
Y-J
YJ
Brewster
M
M
Préat
V
V
D000284:Administration, Oral; D001402:B-Lymphocytes / Q000378:metabolism; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D018920:Coculture Techniques; D004058:Diffusion; D004705:Endocytosis; D020895:Enterocytes / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D008823:Micelles; D008954:Models, Biological; D008970:Molecular Weight; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility
D008823:Micelles; D011091:Polyesters; D011108:Polymers; D011092:Polyethylene Glycols