Synovial fibroblast‐targeting liposomes encapsulating an NF ‐κB‐blocking peptide ameliorates zymosan‐induced synovial inflammation

Abstract Synovial fibroblasts ( SF s) play a crucial role in the inflammatory process of rheumatoid arthritis ( RA ). The highly activated NF ‐κB signal in SF s is responsible for most of the synovial inflammation associated with this disease. In this study, we have developed an SF ‐targeting liposomal system that encapsulates the NF ‐κB‐blocking peptide ( NBD peptide) HAP ‐lipo/ NBD . HAP ‐lipo/ NBD s demonstrated efficient SF ‐specific targeting in vitro and in vivo. Our study also showed a significant inhibitory effect of HAP ‐lipo/ NBD on NF ‐κB activation, inflammatory cytokine release and SF migration capability after zymosan stimulation. Furthermore, the systemic administration of HAP ‐lipo/ NBD s significantly inhibited synovial inflammation and improved the pathological scores of arthritis induced by zymosan. Thus, these results suggest that an SF ‐targeting NF ‐κB‐blocking strategy is a potential approach for the development of alternative, targeted anti‐ RA therapies.