%0 Journal Article
%T Fluorescently Labeled Methyl-Beta-Cyclodextrin Enters Intestinal Epithelial Caco-2 Cells by Fluid-Phase Endocytosis
%A Ferenc Fenyvesi
%A Katalin R谷ti-Nagy
%A Zsolt Bacs車
%A Zsuzsanna Gutay-T車th
%A Milo Malanga
%A 谷va Fenyvesi
%A Lajos Szente
%A Judit V芍radi
%A Zolt芍n Ujhelyi
%A P芍lma Feh谷r
%A G芍bor Szab車
%A Mikl車s Vecserny谷s
%A Ildik車 B芍cskay
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0084856
%X Cyclodextrins are widely used excipients for increasing the bioavailability of poorly water-soluble drugs. Their effect on drug absorption in the gastrointestinal tract is explained by their solubility- and permeability-enhancement. The aims of this study were to investigate penetration properties of fluorescently labeled randomly methylated-beta-cyclodextrin (FITC-RAMEB) on Caco-2 cell layer and examine the cellular entry of cyclodextrins on intestinal cells. The permeability of FITC-RAMEB through Caco-2 monolayers was very limited. Using this compound in 0.05 mM concentration the permeability coefficient was 3.35㊣1.29℅10ˋ8 cm/s and its permeability did not change in the presence of 5 mM randomly methylated-beta-cyclodextrin. Despite of the low permeability, cellular accumulation of FITC-RAMEB in cytoplasmic vesicles was significant and showed strong time and concentration dependence, similar to the characteristics of the macropinocytosis marker Lucifer Yellow. The internalization process was fully inhibited at 0∼C and it was drastically reduced at 37∼C applying rottlerin, an inhibitor of macropinocytosis. Notably, FITC-RAMEB colocalized with the early endosome organizer Rab5a. These results have revealed that FITC-RAMEB is able to enter intestinal epithelial cells by fluid-phase endocytosis from the apical side. This mechanism can be an additional process which helps to overcome the intestinal barrier and contributes to the bioavailability enhancement of cyclodextrins.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0084856