Exosome-inspired liposomal nanocarriers for precision methotrexate delivery in rheumatoid arthritis

Rheumatoid arthritis (RA) is a progressive autoimmune disorder marked by synovial inflammation and cartilage erosion. Conventional methotrexate (MTX) therapy suffers from poor joint targeting and systemic toxicity. This study developed exosome-mimicking liposomes (EMLs) for precision MTX delivery. The optimised formulation (F8), as determined by a 3² factorial design, had vesicle size of 101.4 ± 2.3 nm, encapsulation efficiency (EE) of 82.6 ± 2.4% and a zeta potential of -30.7 ± 1.2 mV. For 24 h, EMLs gave a consistent release pattern (73.4%), matching the kinetics observed using the Korsmeyer-Peppas model (R² = 0.991). MTX taken up by cells was increased approximately 6-7 times higher than free MTX in RAW 264.7 cells. An in vivo study found that EMLs reached a C_max value of 9.6 ± 0.48 µg/mL, had an AUC_0-∞ of 54.3 ± 2.8 µg h/mL and showed 76.8% reduction in paw oedema in collagen-induced arthritis animals. Histopathology analysis found that joints were better protected and there was decreased inflammation and cartilage damage. The results show that EMLs are a reliable and biocompatible way to carry out safe, effective and targeted treatment of RA.