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

Abstract

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-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.

Graphical Abstracts

Keywords:

• Etoricoxib
• rheumatoid arthritis
• artificial neural network
• chondroitin sulphate
• polyelectrolyte complex
• transdermal delivery

Acknowledgment

We sincerely thank DBK pharmaceutical company, Egypt for providing a free sample of ETR, which was used in working on this manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The work presented in this manuscript received no external funding or specific grant from any funding agency in the public, commercial, or not-for-profit sectors. With the exception of ETR, which was provided as a free sample by DBK pharmaceutical company, Egypt, all other aspects of this study were conducted with the sole support of the authors’ personal resources and the facilities provided by their institutions.