| Autor: |
Quan YS; Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan., Hattori K, Lundborg E, Fujita T, Murakami M, Muranishi S, Yamamoto A |
| Jazyk: |
angličtina |
| Zdroj: |
Biological & pharmaceutical bulletin [Biol Pharm Bull] 1998 Jun; Vol. 21 (6), pp. 615-20. |
| DOI: |
10.1248/bpb.21.615 |
| Abstrakt: |
We studied the enhancing and toxic effects of five different absorption enhancers on the transport of FITC-dextran with an average molecular weight of 4000 (FD-4) across Caco-2 cell monolayers, and their enhancing effects were also compared with those in rat intestine. The enhancing and cytotoxic properties of these enhancers were characterized using the following tests: measurement of the permeability coefficients of FD-4 and the transepithelial electrical resistance (TEER) in Caco-2, the release of cytosolic lactate dehydrogenase (LDH) and intracellular mitochondrial dehydrogenase (MDH) activity. All the absorption enhancers increased the permeability of FD-4 across Caco-2 cell monolayers and a good relationship was observed between the enhancement and their toxic effects. However, EDTA and Na-Cap were effective for improving the transport of FD-4 across Caco-2 cells without serious cytotoxicity. At concentrations with low cytotoxicity, various absorption enhancers exihibited reversible effects on the TEER values in Caco-2 cell monolayers, except for 50 mM sodium salicylate (Na-Sal). Moreover, we obtained a good correlation between the enhancement of these enhancers in Caco-2 cell monolayers and in rat large intestine. This finding indicated that the effectiveness of absorption enhancers in the Caco-2 monolayer system was similar to an in vivo rat system. Therefore, the screening system using Caco-2 cell monolayers is useful for examining the effectiveness and toxicity of absorption enhancers. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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