Nanocarrier-based delivery systems for tyrosinase inhibitors in skin depigmentation: Mechanistic insights and translational perspectives

Skin hyperpigmentation disorders, including melasma, post-inflammatory hyperpigmentation, and solar lentigines, impose substantial dermatological and psychosocial burdens and are driven largely by dysregulated melanogenesis and tyrosinase activity. Despite extensive use of conventional depigmenting agents, clinical translation remains limited by poor skin penetration, chemical instability, insufficient selectivity for human tyrosinase, and safety concerns that have led to regulatory restrictions on several agents. Nanotechnology offers a promising paradigm to address these barriers by enabling enhanced drug stability, skin permeation, controlled release, site-specific delivery, and reduced off-target toxicity. This review critically examines the structural architecture, catalytic mechanism, redox behavior, and inhibition kinetics of tyrosinase, with particular emphasis on the molecular determinants that govern inhibitor specificity across human and non-human tyrosinase isoforms. We systematically evaluate advances in nano-enabled delivery of synthetic and natural tyrosinase inhibitors, integrating evidence from biochemical and cellular models, ex vivo skin permeation studies, and clinical investigations to assess therapeutic efficacy and translational readiness. Particular attention is given to formulation–function relationships, biological barriers, nanotoxicological risks, and regulatory considerations governing the development of nano-cosmeceuticals across major jurisdictions. Beyond current approaches, emerging opportunities involving stimuli-responsive nanocarriers, multi-target combination strategies, and artificial intelligence-assisted formulation optimization are discussed as potential routes toward precision depigmentation. Collectively, this review establishes a mechanistic and translational framework for advancing nanocarrier-enabled tyrosinase inhibition from experimental platforms toward safer, more selective, reproducible, and clinically relevant depigmentation therapies.