Combined Ultrasound and Microneedle for Enhanced Transdermal Delivery: Synergistic Mechanisms and Therapeutic Advances

Abstract

Transdermal drug delivery (TDD) offers a non-invasive alternative to conventional administration routes, yet the efficacy of TDD is constrained by the impermeable stratum corneum (SC) of the skin, particularly for macromolecules exceeding 500 Da. While microneedle technology addresses this barrier by creating micro-scale channels, the limited penetration depth of microneedles restricts drug delivery to superficial epidermal layers. This review highlights the transformative potential of combining ultrasound and microneedles for enhanced TDD, which synergistically integrate physical disruption and energy-driven permeation enhancement. Unlike material-based or charge/magnetism-dependent strategies, ultrasound leverages multifactorial mechanisms (mechanical stress, cavitation, and thermal effects) to propel drugs through microneedle-generated pathways into deeper tissues. The ultrasound-microneedle (US-MN) system enables spatiotemporally controlled drug release with sonochemical/piezoelectric effects expanding applications in precision medicine. The underlying mechanisms, technological innovations, and clinical translation challenges of the US-MN have been critically evaluated herein, emphasizing the versatility for macromolecules and precision medicine. By bridging mechanisms with translational gaps, this work provides a roadmap for optimizing the US-MN platform, offering researchers actionable strategies to advance TDD for chronic diseases, vaccines, and targeted therapies.

Keywords

Drug delivery / microneedle / transdermal therapeutic strategies / ultrasound / ultrasound-assisted microneedle

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