Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis. Current therapeutic agents are limited by low bioavailability and multiple adverse effects. Tripterygium glycosides exhibit significant efficacy against RA, but their poor water solubility and pronounced first-pass effect restrict clinical application. To enhance drug delivery efficiency, this study developed a tripterygium glycoside-loaded hydrogel patch based on a transdermal drug delivery system.

The matrix formulation was optimized through single-factor experiments combined with response surface methodology (RSM) to determine the optimal composition. Physicochemical characterization and in vitro drug release studies confirmed that the drug-loaded hydrogel possesses a uniform porous structure, excellent viscoelasticity, and favorable drug release performance. Molecular dynamics (MD) simulations revealed that the system reached equilibrium within 500 ps, with a density of approximately 1.5 g/cm³. The diffusion coefficient of tripterygium glycosides was determined as 1.283×10⁻³ Ų/ps. Radial distribution function (RDF) analysis identified potential atomic interaction distances.

In a complete Freund's adjuvant (CFA)-induced RA mouse model, the high-dose patch (300 mg/kg·d) significantly reduced the arthritis index ，which is a 69.2% reduction compared to the model group，and suppressed serum levels of pro-inflammatory cytokines TNF-α and IL-1β significantly. Hematoxylin and eosin (H&E) staining demonstrated attenuation of synovial hyperplasia and inflammatory infiltration.

This study pioneers the integration of tripterygium glycosides with hydrogel patch technology, effectively overcoming limitations of poor water solubility and low bioavailability of its active components. It provides a novel strategy for the modernization of traditional Chinese medicine