Mannose-modified celastrol liposomes targeted activated macrophages for rheumatoid arthritis treatment in vitro and in vivo evaluation

Rheumatoid arthritis (RA) is an autoimmune illness characterized by symmetrical polyarthritis as the primary clinical symptom. A substantial number of synovial macrophages are activated in RA patients, resulting in synovial inflammation, joint inflammation, and cartilage degradation. The goal of this study is to develop a novel therapy for the effective treatment of RA. We prepared mannose-modified celastrol liposomes (MAN-CSL-lips) by thin-film hydration method. The particle size of the prepared liposomes was (95.37 ± 0.16) nm, and the zeta potential was (−5.4 ± 0.40) mV. The experimental results showed that MAN-CSL-lips had low cytotoxicity and could be efficiently taken up by macrophages, suppress osteoclast formation, and reduce the level of inflammatory factors. In addition, in vivo animal experiments, liposomes can prolong the systemic circulation time of drugs, reduce the joint score and serum inflammatory factor expression in arthritic rats, and have significant cartilage protection and anti-inflammatory effects, making it a promising therapeutic method for treating RA.