Nanocrystal-Based Hydrogels for Cutaneous Delivery: Advances from Fundamental Science to Translational Applications

Nanocrystal-loaded hydrogels (NbHs) have emerged as a promising formulation strategy for cutaneous delivery of poorly water-soluble drugs, synergistically integrating the solubilization and permeation-enhancing advantages of nanocrystals (NCs) with the favorable application properties of hydrogel matrices. This review provides a systematic and translational overview of recent advances in this emerging field. We first elucidate the fundamental mechanisms by which NbHs enhance skin delivery, including concentration gradient-driven diffusion, high drug loading, follicular targeting, and improved chemical stability. We then critically evaluate preparation strategies, covering top-down and bottom-up NC fabrication methods as well as two principal incorporation approaches: in situ gelation and blending incorporation. Furthermore, we provide a comprehensive overview of therapeutic applications, ranging from arthritis and cosmetic formulations to the treatment of psoriasis, androgenetic alopecia, wound healing, atopic dermatitis, cutaneous malignancies, and fungal infections. Finally, we identify critical challenges and future directions, including stability issues, safety evaluation, scalable manufacturing, and the translational gap between pharmaceutical innovation and clinical application. This review aims to provide a “bench-to-bedside” perspective that bridges fundamental science and translational applications, offering valuable insights for the rational design and clinical development of NbHs.