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

Abstract

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 cyp450 (cyp2c29 and cyp2d9) and ugt (ugt2b1) 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 cyp2c29 gene expression, cyp2d9 and ugt2b1 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.