Transdermal drug delivery is a prospective drug delivery strategy to complement the limitations of conventional drug delivery systems including oral and injectable methods. This delivery route allows both convenient and painless drug delivery and a sustained release profile with reduced side effects. However, physiological barriers in the skin undermine the delivery efficiency of conventional patches, limiting drug candidates to small-molecules and lipophilic drugs. Recently, transdermal drug delivery technology has advanced from unsophisticated methods simply relying on natural diffusion to drug releasing systems that dynamically respond to external stimuli. Furthermore, physical barriers in the skin have been overcome using microneedles, and controlled delivery by wearable biosensors has been enabled ultimately. In this review, we classify the evolution of advanced drug delivery strategies based on generations and provide a comprehensive overview. Finally, the recent progress in advanced diagnosis and therapy through customized drug delivery systems based on real-time analysis of physiological cues is highlighted.

透皮药物输送是一种前瞻性的药物输送策略，可以弥补常规药物输送系统（包括口服和注射方法）的局限性。该递送途径允许方便且无痛的药物递送以及具有减少的副作用的持续释放曲线。然而，皮肤中的生理屏障破坏了常规贴剂的递送效率，从而使候选药物限于小分子和亲脂性药物。近来，透皮药物递送技术已经从仅依靠自然扩散的复杂方法发展为对外部刺激动态响应的药物释放系统。此外，使用微针已克服了皮肤中的物理障碍，并且最终使可穿戴生物传感器实现了受控递送。在这篇评论中，我们基于代对先进的药物输送策略的发展进行分类，并提供全面的概述。最后，强调了通过基于生理线索实时分析的定制药物输送系统进行高级诊断和治疗的最新进展。