%0 Journal Article
%T Mechanistic Studies on the Absorption-Enhancing Effects of Gemini Surfactant on the Intestinal Absorption of Poorly Absorbed Hydrophilic Drugs in Rats
%A Akira Yamamoto
%A Hidemasa Katsumi
%A Kosuke Kusamori
%A Masaki Morishita
%A Tammam Alama
%A Toshiyasu Sakane
%J Archive of "Pharmaceutics".
%D 2019
%R 10.3390/pharmaceutics11040170
%X Generally, the use of absorption enhancers might be the most effective approaches to ameliorate the enteric absorption of poorly absorbed substances. Among numerous absorption enhancers, we already reported that a gemini surfactant, sodium dilauramidoglutamide lysine (SLG-30) with two hydrophobic and two hydrophilic moieties, is a novel and promising adjuvant with a high potency in improving the absorption safely. Here, we examined and elucidated the absorption-improving mechanisms of SLG-30 in the enteric absorption of substances. SLG-30 increased the intestinal absorption of 5(6)-carboxyfluorescein (CF) to a greater level than the typical absorption enhancers, including sodium glycocholate and sodium laurate, as evaluated by an in situ closed-loop method. Furthermore, SLG-30 significantly lowered the fluorescence anisotropy of dansyl chloride (DNS-Cl), suggesting that it might increase the fluidity of protein sections in the intestinal cell membranes. Moreover, SLG-30 significantly lowered the transepithelial-electrical resistance (TEER) values of Caco-2 cells, suggesting that it might open the tight junctions (TJs) between the enteric epithelial cells. Additionally, the levels of claudin-1 and claudin-4 expression decreased in the presence of SLG-30. These outcomes propose that SLG-30 might improve the enteric transport of poorly absorbed substances through both transcellular and paracellular routes
%K absorption enhancer
%K gemini surfactant
%K intestinal absorption
%K poorly absorbed drug
%K Caco-2 cells
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523531/