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

J Control Release. 2007 Dec 20;124(3):134-43. doi: 10.1016/j.jconrel.2007.09.001. Epub 2007 Sep 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • B-Lymphocytes / metabolism
  • Biological Availability
  • Biological Transport / drug effects
  • Caco-2 Cells
  • Coculture Techniques
  • Diffusion
  • Endocytosis
  • Enterocytes / metabolism
  • Humans
  • Intestinal Absorption*
  • Micelles*
  • Models, Biological
  • Molecular Weight
  • Particle Size
  • Polyesters / administration & dosage
  • Polyesters / chemical synthesis
  • Polyesters / chemistry*
  • Polyesters / pharmacology
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry*
  • Polyethylene Glycols / pharmacology
  • Polymers / administration & dosage
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Polymers / pharmacology
  • Solubility

Substances

  • Micelles
  • Polyesters
  • Polymers
  • Polyethylene Glycols