Targeted Macrophage Re-programming: Synergistic Therapy with Methotrexate and RELA siRNA Folate-Liposome in RAW264.7 Cells and Arthritic Rats.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation and destruction. Current treatments, like Methotrexate (MTX), though effective, often face limitations such as high plasma C max and lack of sustained release. This study explores a synergistic approach to RA therapy using folate-liposomal co-delivery of MTX and RELA siRNA, targeting RAW264.7 macrophage repolarization via NF-κB pathway inhibition. Extensive in-vitro characterizations demonstrate the stability and biocompatibility of this therapy via folate-liposomes. In the collagen-induced arthritis (CIA) rat model, treatment led to reduced synovial inflammation and improved mobility. The combined MTX and RELA siRNA approach indirectly inhibits inflammatory cytokines, Rheumatoid factor (RF), and C-reactive protein (CRP). Targeted macrophage delivery shows marked therapeutic effects in RAW264.7 murine macrophages, potentially modulating M1 to M2 polarization. This research presents a promising avenue for innovative RA therapies by inhibiting the inflammatory cascade and preventing joint damage. This article is protected by copyright. All rights reserved.