Wearable low-frequency ultrasound for transdermal drug delivery: from mechanisms to clinical translation.

Transdermal drug delivery (TDD) bypasses gastrointestinal degradation and hepatic first-pass metabolism, improving compliance and enabling sustained administration. However, the stratum corneum severely limits the permeation of most hydrophilic and macromolecular drugs. Low-frequency ultrasound (LFU) enhances skin permeability via cavitation and mechanical effects, offering a controllable strategy for overcoming this barrier. Recent advances in flexible electronics have facilitated the development of wearable low-frequency ultrasound patches. This review summarizes the mechanisms, engineering design, applications, and translational challenges of wearable low-frequency ultrasound patches in TDD. A systematic literature search of PubMed, Web of Science, Embase, Scopus, and the Cochrane Library was used to inform a structured narrative review. The scope encompassed English-language articles published from database inception through May 1, 2026, incorporating both primary and secondary studies to conduct a narrative review. Wearable low-frequency ultrasound patches provide a non-invasive and adjustable enhancement strategy for transdermal delivery, particularly for poorly permeable drugs, although current clinical evidence remains largely limited to small studies. Most mechanistic insights are derived from proximate and analogous evidence. Clinical translation requires standardized safety evaluation, reproducibility validation, scalable manufacturing, and clearer regulatory pathways. Future studies should focus on matching acoustic parameters to drug characteristics and improving the long-term safety and reproducibility of wearable delivery systems.