Alama Tammam, Kusamori Kosuke, Morishita Masaki, Katsumi Hidemasa, Sakane Toshiyasu, Yamamoto Akira
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Pharmaceutics. 2019 Apr 7;11(4):170. doi: 10.3390/pharmaceutics11040170.
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 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.
一般来说，使用吸收促进剂可能是改善难吸收物质肠道吸收的最有效方法。在众多吸收促进剂中，我们已经报道过一种双子表面活性剂——二月桂酰胺谷氨酸赖氨酸钠（SLG - 30），它具有两个疏水部分和两个亲水部分，是一种新型且有前景的佐剂，在安全提高吸收方面具有高效能。在此，我们研究并阐明了SLG - 30在物质肠道吸收中的吸收改善机制。通过闭环法评估，SLG - 30使5(6)-羧基荧光素（CF）的肠道吸收增加到比典型吸收促进剂（包括甘氨胆酸钠和月桂酸钠）更高的水平。此外，SLG - 30显著降低了丹磺酰氯（DNS - Cl）的荧光 anisotropy，表明它可能增加肠道细胞膜中蛋白质部分的流动性。而且，SLG - 30显著降低了Caco - 2细胞的跨上皮电阻（TEER）值，表明它可能打开肠道上皮细胞之间的紧密连接（TJ）。另外，在SLG - 30存在的情况下，claudin - 1和claudin - 4的表达水平下降。这些结果表明，SLG - 30可能通过跨细胞和细胞旁途径改善难吸收物质的肠道转运。
