Intraarticular injection of infliximab-loaded thermosensitive hydrogel alleviates pain and protects cartilage in rheumatoid arthritis

Abstract

Purpose: Pain and cartilage destruction caused by rheumatoid arthritis (RA) are major challenges during clinical treatment. Traditional systemic administration not only has obvious side effects but also provides limited relief for local symptoms in major joints. Local delivery of therapeutics for RA treatment is a potential strategy but is limited by rapid intraarticular release. Materials and Methods: In this study, we prepared a thermoresponsive injectable hydrogel by mixing pluronic F127 (F127) and hyaluronic acid (HA) with poly (?-glutamic acid) (PGA) incorporating infliximab (IFX), a new generation monoclonal antibody drug. We investigated the biocompatibility of the hydrogel and its IFX release profile. In vivo, we studied the clinical manifestations (articular skin temperature and joint diameter), detected cytokines in the synovial fluid and cartilage, performed behavioral studies on pain relief, and evaluated the cartilage protection effect. Results: A thermoresponsive hydrogel was successfully prepared by mixing F127, HA, and PGA with injectable properties. The F127-HA-PGA hydrogel had a porous structure with interconnected pores. The infliximab-loaded thermosensitive hydrogel exhibited good bio- compatibility and biodegradability and sustained release properties. Intraarticular injection of the IFX-loaded F127-HA-PGA hydrogel could alleviate the expression of inflammatory cytokines, such as tumor necrosis factor-a (TNF-a), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17), in the synovial fluid and cartilage as well as relieve pain and inhibit cartilage destruction in RA. Conclusion: The double effect on pain relief and cartilage protection indicated the sig- nificant potential of the IFX-loaded injectable hydrogel for RA treatment in major joint lesions.