Methotrexate multivesicular liposome sustained alleviates rheumatoid arthritis in rats

Rheumatoid arthritis (RA) is a chronic inflammatory disease that can cause progressive joint damage. Although methotrexate (MTX) is a first-line treatment for RA, conventional administration may cause systemic adverse effects, highlighting the need for sustained local drug delivery. This study aimed to develop MTX-loaded multivesicular liposomes (MTX-MVLs) for sustained intra-articular delivery and improved RA treatment. MTX-MVLs were prepared using a double-emulsion method and optimized for formulation and process parameters. Their physicochemical properties, in vitro drug release, therapeutic efficacy, joint retention, and systemic safety were evaluated. The optimized MTX-MVLs exhibited high drug encapsulation efficiency and sustained drug release. In an adjuvant-induced arthritis rat model, a single weekly intra-articular injection of MTX-MVLs achieved therapeutic efficacy comparable to biweekly injections of free MTX, while reducing joint swelling and pro-inflammatory cytokine levels. MTX-MVLs also demonstrated prolonged joint retention and a favorable organ safety profile. These findings suggest that MTX-MVLs may provide a promising sustained-release platform for local MTX delivery and warrant further investigation for RA treatment.