Co-delivery of methotrexate and curcumin in hyaluronic acid-coated solid lipid nanoparticles for enhanced anti-rheumatic activity in carrageenan-induced arthritis

초록

Purpose The anti-rheumatic efficacy of methotrexate (MTX) is often compromised by its unfavorable physicochemical properties and hepatotoxic effects. In this study, methotrexate and curcumin co-loaded solid lipid nanoparticles coated with hyaluronic acid (HA-MTX-CUR-SLNs) were developed for more effective rheumatoid arthritis therapy.Methods MTX-CUR-SLNs were prepared using a lipid film hydration technique with a solid lipid (stearic acid), an emulsifier (soy phosphatidylcholine), and a cationic surfactant (CTAB). The optimized MTX-CUR-SLNs were then surface-coated with anionic hyaluronic acid through electrostatic deposition to form HA-MTX-CUR-SLNs, which were characterized for physicochemical properties, morphology, solid-state characteristics, and in vitro release. The in vivo anti-rheumatic activity of HA-MTX-CUR-SLNs was evaluated in rats using a carrageenan-induced arthritis model.Results The optimized MTX-CUR-SLNs had a small particle size (111.4 nm), positive zeta potential (+ 26 mV), spherical shape, and high encapsulation efficiencies for MTX (91%) and CUR (77%). Whereas, HA-MTX-CUR-SLNs showed nanometric size (160 nm), negative surface charge (-22.5 mV) and high MTX (86%) and CUR (72%) encapsulation efficiency. The in vitro release profile showed slower MTX and CUR release from HA-MTX-CUR-SLNs than from drug dispersions. HA-MTX-CUR-SLNs alleviated the severity of carrageenan-induced arthritis by decreasing the joint diameter (0.66 cm) compared to the untreated control (0.84 cm) and MTX-treated (0.79 cm) rats. Furthermore, HA-MTX-CUR-SLNs reduced the liver enzyme levels (ALT and AST) in the serum, thereby demonstrating a reduction in hepatotoxicity.Conclusion Our findings suggest that HA-MTX-CUR-SLNs with enhanced anti-inflammatory activity and reduced hepatotoxicity could be a promising formulation for the efficient treatment of arthritis.

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