Novel vanillic acid-loaded <i>in situ</i> gels: development, characterization, <i>in vitro</i> evaluation for enhanced wound healing and skin irritation test

This study aimed to develop <i>in situ</i> gel formulations containing vanillic acid to enhance patient compliance and accelerate wound healing. Vanillic acid-loaded <i>in situ</i> gels were prepared, and their physicochemical properties were evaluated through <i>in vitro</i> release and <i>ex vivo</i> 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 <i>in vitro</i> over 6 h 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 <i>in situ</i> gels hold promising potential in wound treatment due to their sustained release over 48 h.