The mode of enhanced enteral absorption of macromolecules by lipid-surfactant mixed micelles. I.

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The enhancement of absorption of water soluble macromolecules by lipidsurfactant mixed micelles (MM) was performed in two in vitro experimental systems using rat large intestine, which were isolated epithelial cells containing transcellular route alone and everted sac involving trans- and paracellular routes. Four kinds of fluorescein isothiocyanate-labelled dextrans (FDs) having different average molecular weights (9K-70K) were used as models of water soluble macromolecules. In the absence of MM, very poor transport of FDs was observed in both isolated epithelial cells and everted sac experiments. Linoleic acid-polyoxyethylated (60 mol) hydrogenated castor oil (HCO60) MM enhanced the transport of FDs in both systems, especially for smaller size FDs. This promotive effect by MM decreased with an increase in molecular weight of FDs in both systems. Although enhanced transport of the largest FD (molecular weight, 70K) by MM was clearly demonstrated in the everted sac, the enhanced transport of the same FD in the isolated cells was negligible. These results suggest the possibility of participation of paracellular route as well as transcellular route in the enhancing effect of MM on the large intestinal absorption of water soluble macromolecules.

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