Simultaneous Use of Sodium Deoxycholate and Dipotassium Glycyrrhizinate Enhances the Cellular Transport of Poorly Absorbed Compounds Across Caco-2 Cell Monolayers

Abstract

The absorption-enhancing effect of a combination of sodium deoxycholate and dipotassium glycyrrhizinate in Caco-2 cell monolayers has been compared with that of the enhancers when used alone, and the mechanism of the enhancement was partially elucidated. The effect of the combined compounds was evaluated by measurement of transepithelial electrical resistance (TEER) and the cellular permeability of the water-soluble model compounds sodium fluorescein (MW 376.3) and fluorescein isothiocyanate dextran (MW 4400). The TEER of the monolayers decreased with increasing concentrations of dipotassium glycyrrhizinate in combination with 0.02% (w/v) sodium deoxycholate for 20 min, and reached a minimum at 1% (w/v) dipotassium glycyrrhizinate. Although a combination of 0.02% (w/v) sodium deoxycholate and 1% (w/v) dipotassium glycyrrhizinate enhanced the cellular permeability of sodium fluorescein and fluorescein isothiocyanate dextran, 0.02% (w/v) sodium deoxycholate and 1% (w/v) dipotassium glycyrrhizinate alone had no effect on either the TEER of the monolayers or the cellular transport of the water-soluble compounds. Sequential and separate exposure of the monolayers to each enhancer for 10 min had no effect on the TEER, but a marked decrease in TEER was observed when both compounds were used in combination. The enhancing effect of the combination of sodium deoxycholate and dipotassium glycyrrhizinate was inhibited by H7, a protein kinase C (PKC) inhibitor, suggesting that dipotassium glycyrrhizinate might enhance the activation of PKC via sodium deoxycholate. The combined use of these two enhancers had no toxic effects. These results provide useful, basic information on the action of these absorption enhancers on drugs for which absorption is limited owing to polarity or molecular size, or both.

Bioavailability enhancers of herbal origin: An overview

“…Glycyrrhizin showed a more potent absorption enhancing activity than caproic acid at the same concentration tested [58] . The absorption-enhancing activity obtained from the simultaneous treatment of sodium deoxycholate and dipotassium-glycyrrhizin was much greater than sodium deoxycholate alone in Caco-2 cell monolayers [59] . The absorption enhancing activity of glycyrrhizin was increased by presence of the other absorption enhancers [58] .…”

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“…Glycyrrhizin has shown to possess absorption enhancing (bioavailability enhancing) activity 99,100 . Plumbagin is a natural bicyclic naphthoquinone derived from roots of P. zeylanica.…”

Doxorubicin release from self-assembled nanoparticles of deoxycholic acid-conjugated dextran

“…From these points of view, we synthesized DA-conjugated dextran to make nanoparticles. Since sodium salt of DA is able to form mixed micelle, DA is frequently used as a biocompatible surfactant in the pharmaceutical industry (Walsh and Atkinson, 1986;Sakai et al, 1999;Watanabe et al, 2000).…”

“…Since dextran is fully water-soluble, it was modified hydrophobically using deoxycholic acid (DA). DA was selected to modify dextran because of it is one of the most popular absorption enhancer of hydrophobic drug and used as a source of micelle formation with biochemical agents (Walsh and Atkinson, 1986;Sakai et al, 1999;Watanabe et al, 2000). We investigated physicochemical properties of DA-conjugated dextran (DexDA) using nuclear magnetic resonance spectroscopy (NMR), fluorescence spectroscopy, and transmission electron microscopy (TEM).…”