Bile salts enhance the intestinal absorption of lipophilic drug loaded lipid nanocarriers: mechanism and effect in rats.

TitleBile salts enhance the intestinal absorption of lipophilic drug loaded lipid nanocarriers: mechanism and effect in rats.
Publication TypeJournal Article
Year of Publication2013
AuthorsZhang Z, Gao F, Jiang S, Chen L, Liu Z, Yu H, Li Y
JournalInternational journal of pharmaceutics
Volume452
Issue1-2
Pagination374-81
Date Published2013 Aug 16
Abstract

The purpose of this study was to elucidate the effect and possible mechanism of bile salts on the intestinal absorption of lipophilic drug loaded lipid nanocarriers in rats. Effects of sodium cholate (SC) on the characteristics, intestinal absorption, cellular uptake in Caco-2 cell monolayers and intestinal lymphatic transport of candesartan cilexetil loaded lipid nanocarriers (CLN) were investigated to clarify the possible mechanism. The intestinal absorption of candesartan from CLN was evidently improved over 16-fold compared with free drug suspension, and further significantly enhanced 1.79-fold after the addition of SC. The cellular uptake of CLN in Caco-2 cell monolayers at 37̊C and its colocalization with endoplasmic reticulum were obviously increased in the presence of SC. Moreover, the intestinal lymphatic transport of CLN was obviously enhanced by SC. These results implicated that bile salts could improve the cellular uptake of CLN in Caco-2 cell monolayers via the active processes and promote the intestinal absorption of CLN through the intestinal lymphatic pathway. Therefore, bile salts could be an important physiological factor affecting the intestinal absorption of lipophilic drugs loaded lipid nanocarriers.

DOI10.1007/s11030-013-9451-0
Alternate JournalInt J Pharm