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

• DOI: 10.1016/j.nano.2020.102310
• Publication Date: 2020-10-24T23:18:06Z
• Authors: Rui Hu; Shu Liu; Gulinigaer Anwaier; Qinyu Wang; Wanli Shen; Qiang Shen; Rong Qi
• Keywords: Male; 0301 basic medicine; Drug Carriers; Drug Compounding; Temperature; Biological Transport; Epithelial Cells; Lipids; Madin Darby Canine Kidney Cells; Nanostructures; Mice, Inbred C57BL; Rats, Sprague-Dawley; Drug Liberation; Mice; 03 medical and health sciences; Dogs; Drug Stability; Intestinal Absorption; Liver; Non-alcoholic Fatty Liver Disease; Flavanones; Animals

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.