Polyglutamic acid and Pluronic F127-based hydrogel for loading sinomenine hydrochloride liposomes in the treatment of rheumatoid arthritis.

Sinomenine hydrochloride (SNH), a key therapeutic agent for rheumatoid arthritis (RA), is limited by its low bioavailability, rapid metabolism, and frequent dosing requirements. This study innovatively developed a composite delivery system (SNH-Lip@PPGels) based on polyglutamic acid-poloxamer F127 thermosensitive hydrogel-encapsulated liposomes. In vitro drug release conformed to the Korsmeyer-Peppas kinetic model, demonstrating sustained-release characteristics. In vivo studies confirmed that SNH-Lip@PPGels precisely targets the joint cavity, with intra-articular retention exceeding 24 h. The system alleviates joint swelling and tissue damage in RA models by inhibiting M1 macrophage polarization, significantly reducing TNF-α and IL-6 levels while elevating anti-inflammatory IL-10. Notably, the SNH-Lip@PPGels group exhibited no systemic toxicity, with body weight profiles and histopathology tissues comparable to the normal group. This work proposes a novel RA therapeutic strategy integrating localized targeting and biosafety.