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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 2 2  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-β 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.

Chondroitin Sulphate-Chitosan polyelectrolyte complexes for etorocoxib transdermal delivery: in silico , in vitro and in vivo studies