RESUMEN
Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects around 1% globally leading to joint inflammation and disability. Etorocoxib (ETR) is a potent COX-2 inhibitor traditionally used orally to alleviate RA induced inflammation, yet it causes hepatic side effects on prolonged use. This study aims for in silico optimization of ETR polyelectrolyte complex (PEC) utilizing chondroitin sulphate (CS) and chitosan (CH) for transdermal delivery to RA-inflamed joints with a synergistic anti-inflammatory action owing to CS. An artificial neural network (ANN) combined with 22 factorial design was used to optimize the PEC formula according to particle size (PS) and entrapment efficiency (%EE) by varying CS and CH concentrations. The optimum ETR PEC was incorporated in a gel and examined for its in vitro release, ex vivo permeation, in vivo inflammatory biomarkers, and histopathological evaluation in rats. The optimized formula (F3) with 0.1 CH% w/w and 0.5 CS %w/w showed a PS of 214.98 ± 17.24 nm, %EE 75.31 ± 1.67%, and enhanced in vitro release profile, ex vivo permeation and in vivo anti-inflammatory effect compared to ETR gel via suppressing the expression of IL-6, TNF-α, and TGF-ß pro-inflammatory cytokines as well as the additional anti-inflammatory effect of CS. In conclusion, ETR-PEC gel holds promise as transdermal therapy for managing RA-induced inflammation.