Chronic inflammatory skin disorders present a significant medical challenge and require effective drug carriers and treatments. In this study, we explore the innovative use of hydrogels composed of poly(acrylic acid/poly-vinylpyrrolidone/ 2-dimethylamino ethyl methacrylate) poly(AA/PVP/DMAEM) synthesized by gamma-irradiation as a promising drug delivery system for betamethasone dipropionate (BMDP), a drug commonly used in the management of skin diseases. The novelty is the use of such hydrogels as good reversible swelling behavior candidates, carriers for betamethasone dipropionate drug (BMDP) for skin diseases, and the in-vitro anti-inflammatory assessments were performed. The hydrogel exhibits pH-stimuli-responsive behavior particularly at pH 3 and pH 9, demonstrating excellent reversible swelling characteristics. Notably, the cumulative release percentage from poly(AA/PVP/DMAEM)/BMDP reaches 81.3% and 50.4% after 5.5 h at pH 3 and pH 9, respectively. To assess its potential as an anti-inflammatory agent, various in-vitro evaluations including heat -induced membrane stabilization, hypo-tonicity-induced HRBC membrane stabilization, and egg albumin denaturation tests were performed. Our findings revealed concentrationdependent in vitro anti-inflammatory activity of poly(AA/PVP/DMAEM)/BMDP hydrogels. Specifically, these hydrogels safeguard human erythrocyte mem-branes against heat-induced lysis, prevent RBC membrane hemolysis, inhibit protein denaturation, and exhibit superior egg albumin denaturation prevention. Additionally, they significantly enhance radical scavenging activity, reduce reactive oxygen species (ROS), nitric oxide (NO), and thiobarbituric acid reactive substances (TBARS), elevate total antioxidant capacity (TAC) in lipopolysaccharide (LPS)-stimulated A375 cells, and sup-press inflammation-related cytokines, including tumor necrosis factor (TNF-alpha), nuclear factor-kappa (NF-beta), induced nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Furthermore, our results demonstrate the non-toxic nature of these hydrogels, suggesting their potential for prolonged BMDP transport and being considered as a source of bioactive compounds for the treatment of chronic inflammatory skin disorders.
