Nanoencapsulated Curcumin Mitigates Liver Injury and Drug-Metabolizing Enzymes Induction in Diclofenac-Treated Mice.

Curcumin (CUR) is a natural product with known anti-inflammatory, antioxidant, and hepatoprotective properties. The aim of this study was to formulate CUR into a polymeric nanoparticle (NP) formulation and examine its potential hepatoprotective activity in an animal model of diclofenac (DIC)-induced hepatotoxicity. CUR was loaded into polymeric NPs composed of poly(ethylene glycol)-polycaprolactone (PEG-PCL). The optimal CUR NPs were evaluated against DIC-induced hepatotoxicity in mice, by studying the histopathological changes and gene expression of drug-metabolizing ( and ) and () genes in the livers of the animals. The optimal NPs were around 67 nm in diameter with more than 80% loading efficiency and sustained release. Histological findings of mice livers revealed that CUR NPs exhibited a superior hepatoprotective effect compared to free CUR, and both groups reduced DIC-mediated liver tissue injury. While treatment with DIC alone or with CUR and CUR NPs had no effect on gene expression, and genes were upregulated in the DIC-treated group, and this effect was reversed by CUR both as a free drug and as CUR NPs. Our findings present a promising application for nanoencapsulated CUR in the treatment of nonsteroidal anti-inflammatory drugs-induced liver injury and the associated dysregulation in the expression of hepatic drug-metabolizing enzymes.