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Characterization of Drug Transport Through Tight-Junctional Pathway in Caco-2 Monolayer: Comparison with Isolated Rat Jejunum and Colon

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Abstract

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 ethylenediamine-tetraacetate, 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.

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Authors
  1. Yoshihiro Tanaka
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  2. Yoko Taki
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  3. Toshiyasu Sakane
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  4. Tanekazu Nadai
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  5. Hitoshi Sezaki
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  6. Shinji Yamashita
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Tanaka, Y., Taki, Y., Sakane, T. et al. Characterization of Drug Transport Through Tight-Junctional Pathway in Caco-2 Monolayer: Comparison with Isolated Rat Jejunum and Colon. Pharm Res 12, 523–528 (1995). https://doi.org/10.1023/A:1016245711557

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