Formulation and intestinal absorption of naringenin loaded nanostructured lipid carrier and its inhibitory effects on nonalcoholic fatty liver disease
Formulation and intestinal absorption of naringenin loaded nanostructured lipid carrier and its inhibitory effects on nonalcoholic fatty liver disease
复制标题
柚皮素纳米结构脂质载体的制备、肠道吸收及其对非酒精性脂肪肝的抑制作用
DOI：
10.1016/j.nano.2020.102310
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Qi Rong
中科院分区：
文献类型：
--
作者：
Hu Rui;Liu Shu;Anwaier Gulinigaer;Wang Qinyu;Shen Wanli;Shen Qiang;Qi Rong
本研究制备了载柚皮素（NGN）的纳米结构脂质载体（NGN-NLC），并研究了其性质、跨上皮转运、肠道吸收及对蛋氨酸胆碱缺乏（MCD）诱导的小鼠非酒精性脂肪性肝病（NAFLD）的抑制作用。采用乳化蒸发-低温固化法制备的NGN-NLC载药量为22.5 ± 1.7%。在等剂量下，NGN-NLC通过增强网格蛋白途径的胞内转运和逃避p-gp外排，使NGN的释放速率提高3.5倍，并提高了NGN的跨上皮转运和肠吸收;在低8倍的NGN剂量下，显示出相当的药代动力学参数，但肝脏NGN分布增加了1.5倍，MCD饲料诱导的肝脏脂质沉积降低3倍。这些结果表明，NLC制剂显著增加了NGN对NAFLD的抑制作用，因为改善了药物释放速率、经上皮转运和肠吸收，以及提高了口服生物利用度和肝脏NGN分布。
In this study, we prepared naringenin (NGN) loaded nanostructured lipid carrier (NGN-NLC) and investigated its characterizations, transepithelial transport, intestinal absorption and inhibitory effects on nonalcoholic fatty liver disease (NAFLD) induced by a methionine choline deficient (MCD) diet in mice. The NGN-NLC, prepared by a method of emulsion-evaporation plus low temperature-solidification, displayed high drug loading capacity of 22.5 ± 1.7%. Compared to the NGN crude drug, the NGN-NLC, at an equal NGN dose, improved NGN release rate by 3.5-fold and elevated NGN transepithelial transport and intestinal absorption through enhancing intracellular transport of clathrin pathway and escaping p-gp efflux; at an 8-fold lower NGN dose, showed comparable pharmacokinetic parameters, but elevated liver NGN distribution by 1.5-fold, reduced MCD diet-induced hepatic lipid deposition by 3-fold. These results suggest that the NLC formulation significantly increased the inhibitory effects of NGN on NAFLD because of the improved drug release rate, transepithelial transport and intestinal absorption, and the elevated oral bioavailability and liver NGN distribution.