title: Bile salts enhance the intestinal absorption of lipophilic drug loaded lipid nanocarriers: mechanism and effect in rats.
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.
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.forename: Shijun
authors.initials: S
authors.lastname: Jiang
authors.forename: Lingli
authors.initials: L
authors.lastname: Chen
authors.forename: Zeying
authors.initials: Z
authors.lastname: Liu
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000737:chemistry; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000737:chemistry; D018938:Caco-2 Cells; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D054709:Lecithins / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D020358:Sodium Cholate / Q000008:administration & dosage*; D013024:Soybean Oil / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D013777:Tetrazoles / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004337:Drug Carriers; D054709:Lecithins; D013229:Stearic Acids; D013777:Tetrazoles; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D013024:Soybean Oil; D020358:Sodium Cholate; C077793:candesartan cilexetil