Development of P(NVCL)-based transdermal patches for sinomenine hydrochloride delivery in gouty arthritis.

Gout is a metabolic disease characterized by hyperuricemia and acute arthritis, with global incidence continuing to rise. This study developed a novel transdermal patch utilizing poly(N-vinyl caprolactam) [P(NVCL)] as a carrier matrix for sinomenine hydrochloride. The optimized patch formulation contained 5 % P(NVCL), 1.0 % glycerol, 1.5 % sodium polyacrylate, and 4.0 % sinomenine hydrochloride. A synergistic permeation enhancer system comprising 3 % azone, 6 % borneol, and 3 % menthol significantly improved transdermal absorption efficiency, achieving 248.6 ± 15.7 μg/cm² cumulative penetration over 24 h. LC-MS analysis confirmed successful systemic drug absorption with detectable plasma concentrations at 24 h post-application. In a monosodium urate crystal-induced gouty arthritis mouse model, the patch showed therapeutic efficacy comparable to colchicine treatment. The treatment significantly reduced foot-plantar swelling and serum inflammatory cytokines including IL-1β, TNF-α, and IL-6. The patch effectively lowered serum uric acid, xanthine oxidase, and adenosine deaminase levels while providing substantial protection to joint and kidney tissues. Immunohistochemical analysis revealed significant suppression of NF-κB p65 and phosphorylated NF-κB p65 expression in joint tissues, confirming the anti-inflammatory mechanism through NF-κB pathway inhibition. This study demonstrates that P(NVCL)-based transdermal delivery represents an effective approach for gout treatment in the mouse model, providing a foundation for future clinical development.