The isonicotinamide cocrystal promotes inhibitory effects of naringenin on nonalcoholic fatty liver disease in mice

Abstract

Cocrystal formation can increase the solubility and dissolution rate of the poorly water-soluble drugs, thus enhancing their oral absorption and bioavailability. Our previous study demonstrates that a high dose (100 mg/kg) of naringenin (NGN) has a prominent inhibitory effect on nonalcoholic fatty liver disease (NAFLD) in mice. However, NGN is poorly soluble in water and has low oral bioavailability, which greatly limit its application. To increase solubility and dissolution rate of NGN, the naringenin-isonicotinamide cocrystal (NGN-INT) was prepared by solvent volatilization method. Compared to an equal dose (50 mg/kg) of the NGN crude drug, the NGN-INT significantly increased in vitro release rate as well as in vivo gastrointestinal absorption of NGN and thus more significantly alleviated liver deposition of triglycerides (TG) of the NAFLD mice induced by a methionine choline deficient (MCD) diet.