Formulation and intestinal absorption of naringenin loaded nanostructured lipid carrier and its inhibitory effects on nonalcoholic fatty liver disease

• Published in: Nanomedicine 2021-02, Vol.32, p.102310, Article 102310
• Main Authors: Hu, Rui, Liu, Shu, Anwaier, Gulinigaer, Wang, Qinyu, Shen, Wanli, Shen, Qiang, Qi, Rong
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport - drug effects; Dogs; Drug Carriers - chemistry; Drug Compounding; Drug Liberation; Drug Stability; Epithelial Cells - metabolism; Flavanones - chemistry; Flavanones - pharmacokinetics; Flavanones - pharmacology; Flavanones - therapeutic use; Intestinal absorption; Intestinal Absorption - drug effects; Lipids - chemistry; Liver - drug effects; Liver - pathology; Madin Darby Canine Kidney Cells; Male; Mice; Mice, Inbred C57BL; Nanostructured lipid carrier; Nanostructures - chemistry; Naringenin; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - prevention & control; Nonalcoholic fatty liver disease; Oral pharmacokinetics; Rats; Rats, Sprague-Dawley; Temperature
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2020.102310

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. The NLC formulation explored in this study can significantly improve drug release rate, transepithelial transport, intestinal absorption, liver distribution, oral bioavailability and liver NGN distribution, and therefore significantly enhances the inhibitory effects of NGN on NAFLD. [Display omitted]