Novel Vanillic Acid-Loaded In Situ Gels: Development, Characterization, In Vitro Evaluation for Enhanced Wound Healing and Skin Irritation Test.

Abstract

This study aimed to develop in situ gel formulations containing vanillic acid to enhance patient compliance and accelerate wound healing. Vanillic acid-loaded in situ gels were prepared and their physicochemical properties were evaluated through in vitro release and ex vivo permeation studies. Additionally, antioxidant capacity, cytotoxicity, wound healing, prostaglandin E2 levels, IL-6 inhibition and skin irritation tests were conducted. The optimized IN3-VA formulation exhibited a gelling temperature of 32.394 ± 0.842, a pH value of 4.780 ± 0.010 and a viscosity of 2473.33 ± 11.54 cP. It demonstrated specific mechanical properties, including hardness of 27.94 ± 1.30 g and adhesiveness of -97.00 ± 14.60 g.mm. The IN15-VA formulation showed improved parameters, with a hardness of 38.84 ± 3.33 g, adhesiveness of -126.35 ± 22.78 g.mm, pH value of 4.870 ± 0.010, viscosity of 3853.33 ± 30.55 cP and a gelling temperature of 31.854 ± 0.345. Both formulations demonstrated sustained release behavior, releasing 60% of the medication in vitro over 6 hours with no cytotoxic effects. They also decreased copper ion reduction and the release of nitric oxide, with cellular proliferation rates of 63% for IN3-VA and 73% for IN15-VA. Moreover, IN15-VA significantly reduced prostaglandin E2 levels, controlled IL-6 increase and exhibited non-irritating properties. The results suggest that these vanillic acid-loaded in situ gels hold promising potential in wound treatment due to their sustained release over 48 hours.