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.

在本研究中，我们制备了负载柚皮素 (NGN) 的纳米结构脂质载体 (NGN-NLC)，并研究了其特性、跨上皮转运、肠道吸收和对蛋氨酸胆碱缺乏 (MCD) 饮食诱导的非酒精性脂肪肝 (NAFLD) 的抑制作用在老鼠身上。NGN-NLC采用乳液蒸发加低温固化的方法制备，载药量高达22.5±1.7%。与NGN原料药相比，NGN-NLC在同等NGN剂量下，通过增强网格蛋白通路的细胞内转运和逃避p-gp外流，将NGN释放率提高3.5倍，并提高NGN跨上皮转运和肠道吸收；NGN 剂量低 8 倍时，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，将 MCD 饮食诱导的肝脏脂质沉积减少了 3 倍。这些结果表明，NLC 制剂显着增加了 NGN 对 NAFLD 的抑制作用，因为它提高了药物释放速率、跨上皮转运和肠道吸收，以及口服生物利用度和肝脏 NGN 分布的升高。