Rheumatoid arthritis (RA) is a chronic inflammatory disease with progressive and irreversible joint damage. The effectiveness of systemic RA treatments is limited by difficulties in achieving therapeutic doses within articular joints. We evaluated the ability of intra-articular administration of injectable formulations to synergistically enhance repair of RA joints. Methotrexate-loaded hyaluronic acid (Met-HA), dexamethasone-loaded microcapsules (Dex-M), and Dex-M dispersed inside Met-HA (Met-HA/Dex-M) were prepared as viscous emulsions and injected into articular knee joints using a 21-gauge needle to form a drug depot. By near-infrared (NIR) fluorescence imaging replaced with drugs, we confirmed the local release of NIR from the depot injected into the articular joint over an extended period. After in vivo treatment with Dex-M, Met-HA, and Met-HA/Dex-M, RA repair was confirmed by imaging of the feet, micro-CT, and histology. TNF-α expression in all treatment groups was gradually decreased as a function of injection time. In comparison with the subjects treated with Met-HA or Dex-M alone, subjects treated simultaneously with Met-HA and Dex-M exhibited faster and more significant RA repair. Collectively, these results indicated that the drug depot formed after intra-articular injection of Met-HA/Dex-M induced long-lasting drug release and allowed Met and Dex to effectively act in the articular joint, resulting in enhanced RA repair.
