Enhancement of intestinal permeability of Quercetin by nanostructured lipid carriers / 中国药学杂志

ABSTRACT

OBJECTIVE: To elucidate biological characteristics and uptake mechanism of Quercetin-nanostructured lipid carriers (Q-S) in vivo and in vitro. METHODS: Quercetin suspension (Q-X), quercetin-phospholipid complex (Q-L) and nanostructured lipid carriers loaded with quercetin (Q-S) were prepared. Then the intestinal permeability of these three formulations were studied using in situ rat intestinal perfusion, followed by in vivo relative oral bioavailability studies. In addition, in vitro cellular uptake of quercetin from Q-S in a time and concentration-dependent were carried out. To elucidate the uptake mechanism(s) from Q-S, Q-L and Q-X contribution of NPCILI carrier-mediated uptake, endocytosis and passive permeability were investigated. RESULTS: In situ studies demonstrated Q-S has 14-fold higher permeability than Q-X and 3-fold than Q-L. In vivo studies showed Q-S relative oral bioavailability is increased dramatically (Fr=4.6), meanwhile, no significant increased for Q-L compared with Q-X. Consistent with in situ results, in vitro time and concentration-dependent studies revealed quercetin uptake from Q-S was obviously higher than Q-X and Q-L. In vitro mechanistic characterization showed that the reduced contribution of NPCILI to the transport and passive diffusion enhancement of quercetin are primary explanations for its enhanced uptake from Q-S. CONCLUSION: Quercetin can enhance oral bioavailability attributed to enhance passive permeability and reduce transport of NPCILI formed nanostructured lipid carriers.