Transdermal drug delivery: Principles, technologies, therapeutic applications, and future directions

Transdermal drug delivery systems (TDDS), as an important alternative to oral and injectable administration, offer significant advantages including non-invasive delivery, avoidance of first-pass metabolism, and the ability to achieve sustained drug release. However, the physicochemical properties of the skin impose multiple barriers and limitations on transdermal drug delivery, which has motivated extensive research efforts to overcome these bottlenecks. This review focuses on the fundamental principles of transdermal drug transport and summarizes major technological approaches, including passive diffusion systems, active enhancement strategies, microneedle-based delivery platforms, and nanocarrier systems. In addition, recent advances in the application of TDDS for the treatment of skin diseases, immune disorders, neurological diseases, and cardiovascular diseases are reviewed. Finally, key challenges and future perspectives toward intelligent, personalized, and multifunctional TDDS are discussed, with an emphasis on clinical translation issues such as interindividual variability in skin barrier function, formulation design, safety, and regulatory considerations, underscoring the potential of TDDS in modern medicine.