Characterization of drug transport through tight-junctional pathway in Caco-2 monolayer: comparison with isolated rat jejunum and colon.
Drug transport through the tight-junctional pathway in Caco-2 monolayer was studied by examining the relationship between its permeability to hydrophilic drugs and membrane conductance. Compared with the rat isolated jejunum or colon, Caco-2 monolayer displayed high electrical resistance and low conductance, as well as low permeability to sulfanilic acid and FITC-dextran (M.W. 4000). However, there was a linear relationship between the drug permeability and partial Cl- ion conductance for Caco-2 monolayer, rat jejunum and colon. Hence, the permeability to those drugs per unit of Cl- conductance is similar in the three membranes, suggesting that the size (radius) of the tight-junctional pathway in the three membranes is similar. In addition, when the electrical resistance of Caco-2 monolayer was reduced to the same level as that of the jejunum or colon by pretreatment with disodium ethylenediaminetetraacetate, its permeability to FITC-dextran became significantly higher than that of other membranes. Accordingly, the high resistance and the low permeability of Caco-2 monolayer compared with rat intestinal membrane may be due to structural differences between the membranes, rather than a difference in the tightness of the junction.[1]References
- Characterization of drug transport through tight-junctional pathway in Caco-2 monolayer: comparison with isolated rat jejunum and colon. Tanaka, Y., Taki, Y., Sakane, T., Nadai, T., Sezaki, H., Yamashita, S. Pharm. Res. (1995) [Pubmed]
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