Ameliorative effects of chitosan nanoparticles containing a scorpion-derived potassium channel inhibitory peptide (alpha-KTx 3.13) in a juvenile model of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a prevalent autoimmune disorder affecting millions of individuals worldwide, leading to chronic joint inflammation, progressive tissue damage, and substantial impairment of quality of life. In this study, we explored the therapeutic potential of chitosan nanoparticles encapsulating MeuKTx, a potassium channel inhibitory peptide targeting Kv1.3, in modulating articular tissue alterations in a neonatal rat model of RA. The peptide, alpha-KTx 3.13, was synthesized using solid-phase peptide synthesis, followed by purification and characterization through high-performance liquid chromatography (HPLC) and mass spectrometry to ensure its quality and bioactivity. Neonatal Wistar rats were assigned to various experimental groups, including a healthy control, an untreated RA model, and groups treated with methotrexate or peptide-based formulations delivered via chitosan nanoparticles. The treatment groups demonstrated significant reductions in serum malondialdehyde and rheumatoid factor (RF) levels, indicating a decrease in oxidative stress and systemic autoimmune activity. At the molecular level, expression of pro-inflammatory mediators, including transforming growth factor-beta (TGF-β) and monocyte chemoattractant protein-1 (MCP-1/CCL2), as well as Caspase-8 protein levels, were markedly decreased in peptide-treated groups, correlating with improved histopathological outcomes in joint tissues. Notably, the chitosan nanoparticle formulation enhanced the bioavailability and therapeutic efficacy of MeuKTx, suggesting that targeted delivery to Kv1.3 channels can modulate immune and inflammatory responses more effectively than free peptide administration. Collectively, these findings highlight the potential of MeuKTx-loaded chitosan nanoparticles as a novel therapeutic strategy for RA, offering a promising approach to reduce joint inflammation, oxidative stress, and immune dysregulation while potentially minimizing reliance on conventional chemical drugs. This study provides a foundation for further exploration of peptide-based nanotherapies in autoimmune and inflammatory diseases.