Resveratrol-loaded novasomal gel for sustained dermal delivery against monobenzone-induced vitiligo-like depigmentation in black chicks.

Vitiligo is a multifactorial depigmenting disorder characterized by melanocyte loss, oxidative stress, and impaired melanogenesis. Resveratrol (RVT) exhibits potent antioxidant and cytoprotective properties; however, its topical application is limited by its poor cutaneous penetration, rapid degradation, and limited local bioavilability. To overcome these limitations, we developed a resveratrol-loaded novasomal formulation (RVT-NVS) and evaluated its physicochemical properties, in vitro release behavior, repigmentation efficacy in a 40% monobenzone (MZ)-induced vitiligo-like depigmentation model in black chicks. Dermal tolerability was additionally assessed in rats. RVT-NVS exhibited nanoscale vesicles with an average size of 386 nm, a a relatively narrow size distribution (PDI = 0.31), high entrapment efficiency of 79%, and a negative zeta potential of - 37 mV. The RVT-NVS gel showed sustained RVT release over 12 h compared with the free RVT gel. MZ induced marked depigmentation, hematological alterations, reduced body weight gain, histopathological skin damage, reduced tyrosinase immunoreactivity, and altered behavioral readouts. RVT-NVS significantly improved visible repigmentation, normalized hematological parameters, improved body weight gain, preserved epidermal and feather follicle architecture, and restored tyrosinase-positive melanocyte-associated staining more effectively than free RVT, blank nanovehicle, or natural composite formulations. RVT-NVS also improved several MZ-associated behavioral readouts, including sweet-solution consumption, locomotor activity, social-response measures, freezing behavior, and tonic immobility duration. Molecular docking suggested possible interactions of RVT with targets related to redox regulation, melanogenesis, inflammation, and apoptosis, with favorable predicted interactions observed for catalase (CAT) and selected melanogenesis-associated targets. These findings suggest that RVT-NVS may represent a promising nanoscale topical delivery system for chemically induced oxidative melanocyte injury and vitiligo-like depigmentation.