Comparison of different intestinal epithelia as models for absorption enhancement studies.
In this study we compared the effect of two surfactants (laureth-6 and sodium docusate) on the permeability of a model hydrophilic drug across three different epithelia (Caco-2 cells, stripped porcine jejunum and rat ileo-jejunum). Among the tested epithelia Caco-2 cells are the tightest with the trans-epithelial electrical resistance of 372+/-4 Omega cm2 followed by porcine jejunum (124+/-8 Omega cm2) and rat ileo-jejunum (33+/-2 Omega cm2). Both surfactants decreased the trans-epithelial electrical resistance and increased the permeability of a model drug across Caco-2 cells at concentrations as low as 0.02 mg/ml, with more pronounced effect observed for laureth-6. On the other hand, ten times higher concentrations (0.2 mg/ml) did not affect the permeability of the model drug across the porcine jejunum. Similarly, laureth-6 at this high concentration had no effect on the trans-epithelial electrical resistance of the rat ileo-jejunum and did not increase the permeability of the model drug across this tissue. On the basis of these results we concluded that Caco-2 cells are much more sensitive to the investigated surfactants, that act as permeation enhancers, than the native intestinal tissues. Therefore, the results obtained in the experiments with Caco-2 cells might exaggerate the effects of the surfactants on the permeability compared to in vivo situation.
Legen
I
I
Lek Pharmaceuticals d.d., Research and Development, Verovskova 57, 1526 Ljubljana, Slovenia. igor.legen@lek.si
Salobir
M
M
Kerc
J
J
D000818:Animals; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D004143:Dioctyl Sulfosuccinic Acid / Q000493:pharmacokinetics; D006801:Humans; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000737:chemistry / Q000493:pharmacokinetics; D013552:Swine
D013501:Surface-Active Agents; D000077423:Polidocanol; D004143:Dioctyl Sulfosuccinic Acid; D011092:Polyethylene Glycols