Nasra, SimranSimranNasraBhatia, DhirajDhirajBhatiaKumar, AshutoshAshutoshKumar2025-08-312025-08-312024-09-0110.1002/adhm.2024006792-s2.0-85194577206https://d8.irins.org/handle/IITG2025/2875838794813Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation and destruction. Current treatments, such as Methotrexate (MTX), though effective, often face limitations such as high plasma C<inf>max</inf> and lack of sustained release. This study explores a synergistic approach to RA therapy using folate-liposomal co-delivery of MTX and RELA siRNA (short interfering RNA), targeting RAW264.7 macrophage repolarization via nuclear factor kappa B (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 leads 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.falsefolate liposome | inflammation | methotrexate | RELA siRNA | rheumatoid arthritis | synovial macrophagesArticle219226591 September 2024102400679arJournal11WOS:001234205500001