Novel ethosomal gel formulation for enhanced transdermal delivery of curcumin and cyclosporine: a preclinical approach to rheumatoid arthritis management
Sankalp Gharat, Munira Momin, Urvashi Panchal, Abdelwahab Omri
Abstract
Vesicular systems have demonstrated efficacy in the management of Rheumatoid Arthritis (RA). This study explores the synergistic effect of edge-activated ethosomal gel to enhance the transdermal delivery of Curcumin (CUR) and Cyclosporine (CYC). Ethosomal vesicles prepared via the ethanol injection method were incorporated into a gel, with the optimized formulation exhibiting an average particle size of 93.3 ± 1.17 nm and a zeta potential of −29.2 ± 0.17 mV. Ex vivo diffusion studies on porcine ear skin demonstrated 97.115 ± 0.40% CUR and 98.331 ± 1.08% CYC release over 18 hours, exhibiting Hixson-Crowell diffusion mechanisms. The steady-state flux and permeability coefficients were 0.095 µg/cm2/hr and 0.0095 cm/hr for CUR, and 0.0804 µg/cm2/hr and 0.01608 cm/hr for CYC respectively. In anti-inflammatory tests on lipopolysaccharide (LPS)-induced RAW 264.7 cells, the gel significantly increased IL-10 levels (p < 0.001), inhibited prostaglandin-E2, and reduced IL-6 and TNF-α levels (p < 0.001). Moreover, the ethosomal gel demonstrated nonirritating properties and exhibited significant reduction in arthritic symptoms in the Complete Freund’s Adjuvant induced 28-day rat model, surpassing the effects of marketed and conventional gel. These findings highlight the synergistic benefits of combining CUR and CYC in an ethosomal gel, offering a promising alternative for RA management. Future clinical investigations are warranted to validate its safety and efficacy in humans and facilitate potential therapeutic integration.