L-Carnosine loaded chondroitin sulphate functionalized proposomes as an effective tool for transdermal rheumatoid arthritis management

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint inflammation, cartilage deterioration, and oxidative stress. The study developed transdermal RA treatment with L-carnosine (CAR)-loaded chondroitin sulphate (CHS) functionalised proposomes. CHS-functionalised proposomes measured 285 ± 0.89 nm, with PDI of 0.31 ± 0.05, zeta potential of -13.6 ± 0.67 mV, and entrapment efficiency of 73.96 ± 0.87. TEM confirmed their spherical shape and homogenous CHS coating. Biphasic drug release <i>in vitro</i> began with 13.2% burst release in 0.5 h and over 8 h, sustained release reached 83.79%. <i>Ex-vivo</i> permeation results revealed that the selected formulation increased CAR flux by 30.97 folds compared to CAR gel. <i>In vivo</i> testing in rats with AIA model showed that group treated with selected formulation demonstrated reduced joint inflammation and soft tissue swelling that was further confirmed by X-ray radiography. ELISA results showed significant reduction in TNF-α and IL-1β and elevation in NRF2 and SOD with levels comparable to the negative control group. Histopathological investigation showed cartilage integrity and proteoglycan content similar to the negative control. The CHS-functionalised CAR-loaded proposomes improved CAR permeation, targeted inflammatory joints, and reduced oxidative stress, making them a viable non-invasive RA treatment.