Smart responsive microneedles for drug delivery and therapeutic applications.

Drug delivery systems are essential to modern medicine, aiming to transport drugs precisely to target sites for enhancing drug efficacy and reducing corresponding side effects. As an innovative transdermal technology, microneedle (MN)-based drug delivery offers minimal invasiveness, painlessness, and facile control. Smart responsive MNs represent a recent advancement, featuring bio-inspired structures, multilayer designs, flexible substrates, and wearable integration, all of which can improve patient compliance. These MNs can be prepared from various materials, and their structures and functions can be tailored by adjusting their compositions, response mechanisms, and fabrication methods to match specific applications. Upon exposure to specific stimuli, smart responsive MNs enable precise, controllable drug release in complex biological environments. Multi-responsive systems further enhance targeting and release control by integrating multiple stimulus-response pathways. Currently, smart responsive MNs are being explored for drug delivery, vaccination, cosmetics, diagnostics, tissue engineering, cancer therapy, and wound healing. However, reviews in this area remain limited. Accordingly, this review outlines the design strategies, emerging technologies, innovative functions, and clinical uses of smart responsive MNs, while discussing key challenges and future directions. It provides insights to support research on novel MN-based drug delivery and therapy.