Transport mechanisms of mmePEG750P(CL-co-TMC) polymeric micelles across the intestinal barrier
| Autor: | Véronique Préat, Albertina Arien, Marcus E. Brewster, Y.-J. Schneider, A. des Rieux, Frédéric Mathot |
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| Rok vydání: | 2007 |
| Předmět: |
Stereochemistry
Polymers Polyesters Pharmaceutical Science Administration Oral Biological Availability Endocytosis Micelle Models Biological Polyethylene Glycols Diffusion Monolayer Humans Particle Size Lipid bilayer Micelles B-Lymphocytes Tight junction Chemistry Biological Transport Coculture Techniques Molecular Weight Membrane Enterocytes Intestinal Absorption Solubility Caco-2 Paracellular transport Biophysics Caco-2 Cells |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 124(3) |
| ISSN: | 1873-4995 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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