Hyaluronic Acid-Coated Solid Lipid Nanoparticles Enhance Antirheumatic Activity and Reduce Toxicity of Methotrexate

Aim: Methotrexate (MTX) is used to treat rheumatoid arthritis (RA) but is associated with severe toxicity. To minimize these side effects of MTX, the study was undertaken to explore its delivery using solid lipid nanoparticles (SLNs). Materials & methods: MTX-loaded SLNs were synthesized and coated with hyaluronic acid (HA) for targeted drug delivery and evaluated for their safety and efficacy in a complete Freund's adjuvant (CFA) model. Results: HA-MTX-SLNs (230.0 ± 46.4 nm) with 78.75% entrapment were developed and showed sustained drug release with a significant reduction in toxicity and enhanced activity of the drug at the targeted site upon oral administration in CFA-induced rats. Conclusion: HA-MTX-SLNs can be considered as an efficient therapeutic agents for the treatment of RA.Rheumatoid arthritis (RA) is an autoimmune disease of the joints with no cure and treatment modalities only focus on reducing the symptoms. Methotrexate (MTX) is a primary drug used for its treatment but is associated with severe toxicity. The study aimed to use solid lipid nanoparticles (SLNs) as carriers for MTX to achieve improved efficacy in RA treatment at reduced doses, thus decreasing the potential toxicity of the drug, making SLNs suitable and safe drug carriers. MTX-loaded SLNs (MTX-SLNs) were formulated and coated with hyaluronic acid (HA; HA-MTX-SLNs) and were evaluated for their efficacy in a complete Freund's adjuvant (CFA)-induced arthritic rat model. Both MTX-SLNs and HA-MTX-SLNs demonstrated a significant reduction in toxicity and enhanced the activity of the drug upon oral administration. The HA coating further enriched the antirheumatic activity of MTX, owing to its ability to improve the oral bioavailability and targeted drug delivery of the formulation. Thus, HA-MTX-SLNs can be considered efficient therapeutic agents for the treatment of RA.