Precision biomaterials for vitiligo: A translational framework for targeted cutaneous delivery

Vitiligo is a chronic autoimmune pigmentary disorder characterized by melanocyte destruction and progressive depigmentation, frequently associated with substantial psychosocial burden, particularly in individuals with skin of color. Despite recent advances in therapy, including topical ruxolitinib and emerging targeted immunomodulatory approaches, major limitations remain, including incomplete repigmentation, variable therapeutic response, relapse following treatment discontinuation, limited access to phototherapy, and challenges in treating extensive body surface areas. These gaps highlight the need for strategies that improve the localization, durability, and consistency of therapeutic exposure within depigmented lesions. Emerging biomaterial-based approaches, including hydrogels and nanoparticle delivery systems, offer promising opportunities to enhance localized retention and sustained release of topical therapeutics. Chitosan-based systems are particularly attractive due to their biocompatibility, electrostatic interaction with nucleic acids, mucoadhesive properties, and tunable physicochemical characteristics. Modified derivatives such as succinylated chitosan further expand opportunities to regulate hydration behavior, diffusion kinetics, and localized therapeutic retention. Localized nucleic acid delivery approaches, including siRNA and dsRNA-based systems, represent an additional translational strategy for targeted modulation of inflammatory pathways implicated in vitiligo pathogenesis. Chitosan polyplex nanoparticles may provide a platform for protecting nucleic acid cargo while improving localized transport and therapeutic delivery within the cutaneous microenvironment. This narrative review examines the translational potential of chitosan-based hydrogels, N-succinyl chitosan and nucleic acid nanoparticle systems in vitiligo, emphasizing precision topical delivery, skin of color considerations, and future biomaterial strategies aimed at improving repigmentation outcomes and reducing disease burden.