Formulation and Evaluation of thermosensitive drug delivery system containing Methotrexate, Dexamethasone and Meloxicam for rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease that significantly increases morbidity and mortality rates. Although Methotrexate (MTX) is the primary treatment for RA, its side effects often lead to treatment discontinuation. This study aims to develop a thermoresponsive sol-gel drug delivery system using Poloxamer 407 (P407) and Poloxamer 188 (P188) to provide a targeted and sustained release of a combination therapy consisting of MTX, Meloxicam (MLX), and Dexamethasone (DEX) for direct intra-articular administration. Methodology: The thermoresponsive sol-gel system was formulated using P407 and P188 as base polymers. MTX, MLX, and DEX were incorporated into the formulation, which was then evaluated in both in-vitro and in-vivo settings. The drug release profile, therapeutic efficacy, and potential toxicity were assessed to determine the system's effectiveness in RA treatment. Characterization: The developed sol-gel system was characterized based on: Drug loading efficiency, Rheological properties, In-vitro drug release studies over 48 hours, In-vivo therapeutic efficacy using a rat model of rheumatoid arthritis. Results: The thermoresponsive sol-gel system exhibited sustained and controlled drug release over 48 hours, with individual drug release rates of: MTX: 47%, MLX: 52%, DEX: 40%, For the optimized formulation with triple therapy, the release rates were: MTX: 48%, MLX: 49%, DEX: 38%, In in-vivo studies, the sol-gel system significantly delayed disease progression and reduced drug-related toxicities compared to free drug administration. Conclusion: The thermoresponsive sol-gel drug delivery system offers an effective and sustained intra-articular treatment for rheumatoid arthritis, improving therapeutic outcomes while minimizing systemic side effects. This approach presents a promising alternative to conventional RA therapies, ensuring better patient compliance.