Disulfiram encapsulated in polymer nanoparticles ameliorates thioacetamide-induced liver injury

Liver disease is the cause of approximately 2 million deaths per year worldwide. Liver macrophages (Kupffer cells), the most abundant immune cells in the liver, play important roles in innate immunity and contribute to many liver diseases. Disulfiram (DSF), a drug used to treat alcohol abuse, has attracted increasing attention due to its anti-cancer and anti-inflammatory effects. However, DSF accumulates in several cell types, and few studies have examined its utility as a potential treatment for liver injury. Here, we investigated the biological efficacy of DSF encapsulated in poly(lactic-co-glycolic) acid nanoparticles (DSF@PLGA NPs). In vitro, DSF@PLGA NPs had low cytotoxicity, were selectively taken up by the human macrophage cell line THP-1 via macropinocytosis, and inhibited lipopolysaccharide-induced proinflammatory cytokine production by THP-1 cells. Intravenously administered PLGA NPs predominantly localized to the liver, specifically CD68-positive Kupffer cells, and DSF@PLGA NPs significantly ameliorated thioacetamide-induced proinflammatory cytokine production and liver injury. Our results indicate that encapsulation in PLGA NPs promotes specific delivery of DSF to Kupffer cells and reduces liver injury and inflammation, suggesting that DSF@PLGA NPs may be a promising treatment for liver disease.