Revolutionizing transdermal drug delivery evaluation: the evolution from traditional models to skin organoids and the integration of artificial intelligence.

This review examines the evolution of evaluation systems for transdermal drug delivery systems (TDDS) alongside recent advances in skin organoids (SkOs). We discuss the potential of SkOs as in vitro models, with particular attention to their structural complexity and their ability to recapitulate appendage-associated transport pathways more effectively than traditional animal models and reconstructed human epidermis (RHE). We also summarize current fabrication strategies, physiological validation, and the main translational limitations of SkOs. In addition, we discuss how artificial intelligence (AI), computer vision, and digital twin technologies may help address current challenges in standardization and quality control. Self-assembling SkOs derived from induced pluripotent stem cells represent a promising candidate advance for future TDDS evaluation. Although limitations in maturation remain, the integration of SkOs with AI may support the development of a more standardized, high-throughput, and predictive platform for transdermal drug delivery research.