Pulmonary delivery of curcumin-loaded glycyrrhizic acid nanoparticles for anti-inflammatory therapy

Abstract

Acute lung injury (ALI) is an inflammatory disease of the lungs. Curcumin (Cur) shows protective effects in ALI animal models. However, Cur is a hydrophobic drug and its administration into the lungs is inefficient due to its low bioavailability. In this study, glycyrrhizic acid (GA) micelles were produced and evaluated as a carrier of Cur for treatment of ALI. Cur-loaded GA (GA-Cur) nanoparticles were produced using an oil-in-water emulsion/solvent evaporation method. The size and surface charge of the GA-Cur nanoparticles were 159 nm and -23 mV, respectively. In lipopolysaccharide-activated RAW264.7 cells, the GA-Cur nanoparticles decreased the pro-inflammatory cytokine levels more efficiently than GA, Cur, or a simple mixture of GA and Cur (GA + Cur). This suggests that the GA-Cur nanoparticles improved the therapeutic efficiency by enhanced delivery of GA and Cur. GA-Cur inhibited the nuclear translocation of nuclear factor-kappa b and induced endogenous heme oxygenase-1 more efficiently than the other treatments. Furthermore, an in vitro toxicity test showed that GA-Cur had little cytotoxicity. In vivo therapeutic effects of GA-Cur were evaluated in ALI mouse models. GA-Cur was administered into the animals by intratracheal instillation. The results showed that GA-Cur reduced pro-inflammatory cytokines in a dose-dependent manner and did so more efficiently than GA, Cur, or GA + Cur. Furthermore, the hemolysis and infiltration of monocytes into the lungs were more effectively inhibited by GA-Cur than the other treatments. The data indicate that GA is an efficient carrier of Cur and an anti-inflammatory drug. Owing to their delivery efficiency and safety, GA-Cur nanoparticles will be useful for treatment of ALI.