title: Enhanced oral delivery of alendronate by sucrose fatty acids esters in rats and their absorption-enhancing mechanisms.
abstract: Oral delivery is the most fascinating route for interminable drug remedy. However, the intestinal absorption of alendronate (ALN), a bisphosphonate drug after oral administration is very poor. Absorption enhancers, which help to achieve the efficiency-safety balance, are considered one of the most promising agents for the improvement the intestinal absorption of drugs. In the current study, we focused on using sucrose fatty acid esters (SEs) as promising absorption enhancers to enhance the intestinal absorption of alendronate using an in situ closed-loop method in rats. The intestinal absorption of alendronate was significantly enhanced in the presence of SEs, especially L-1695. In addition, no considerable increase was observed in the activity of lactate dehydrogenase (LDH) or in protein release from the intestinal epithelium in the presence of sugar esters at concentrations equivalent to or lower than 1.0% (w/v), suggesting that these compounds are safe. Furthermore, mechanistic studies revealed increased membrane fluidity and loosening of the tight junctions (TJs) might be the underlying mechanism by which SEs improve the intestinal intake of alendronate, via transcellular and paracellular routes, respectively. These findings suggest that SEs are effective absorption enhancers for improving the intestinal absorption of alendronate, without causing serious damage to the enteric epithelium.
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors: Tammam
authors: T
authors: Alama
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors: Hiroko
authors: H
authors: Katayama
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors: Sachiko
authors: S
authors: Hirai
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors: Shizuka
authors: S
authors: Ono
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors: Ayumi
authors: A
authors: Kajiyama
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors: Kosuke
authors: K
authors: Kusamori
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors: Hidemasa
authors: H
authors: Katsumi
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan.
authors: Toshiyasu
authors: T
authors: Sakane
authors: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto 607-8414, Japan. Electronic address: yamamoto@mb.kyoto-phu.ac.jp.
authors: Akira
authors: A
authors: Yamamoto
mesh_terms: D000284:Administration, Oral; D019386:Alendronate / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D004952:Esters / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000737:chemistry*; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D004952:Esters; D005227:Fatty Acids; D011506:Proteins; D013395:Sucrose; D007770:L-Lactate Dehydrogenase; D019386:Alendronate
keywords: Absorption enhancer; Alendronate; Bisphosphonate; Intestinal absorption; Poorly absorbed drug; Sucrose fatty acid ester