Multi-stimuli responsive microneedle systems for precision transdermal therapy

Microneedles (MNs), as a transdermal drug delivery system, not only exhibit superior therapeutic efficacy but also ensure drug stability, holding remarkable advantages over conventional oral or intravenous administration routes. Recent advances in next-generation smart-responsive MN systems have focused on boosting real-time biomedical applicability through the integration of bioinspired, bio-derived, or biocompatible materials. These smart MNs possess unique characteristics, including skin adhesion, tunable dissolution kinetics, and environmental responsiveness, thereby enabling their deployment in wearable biosensors, rapid drug delivery systems, and responsive therapeutic platforms. This review specifically summarizes the progress of various stimulus-responsive MNs (e.g., pH-, temperature-, or electro-activated systems), which dynamically regulate drug release or modulate the therapeutic microenvironment in response to endogenous or exogenous signals such as pH variations, temperature fluctuations, and reactive oxygen species (ROS). Collectively, these smart MN systems open up new avenues for the clinical treatment and management of diabetes, cancer, and chronic cutaneous disorders. • Highlights MN-based TDDS advantages: avoiding oral/hepatic drug degradation, reducing cross-infection, and painless stratum corneum penetration. • Summarizes pH-/temperature-/ROS-responsive smart MNs for dynamic drug release and targeted diabetes/cancer treatment. • Emphasizes biocompatible materials (HA, PLGA, silk) as smart MN frameworks ensuring biomedical safety/functionality. • Highlights MN-combined therapies (PTT/PDT) for significantly enhanced efficacy (e.g., improved tumor suppression). • Addresses multi-stimuli therapy integration gaps via smart MNs for precise drug delivery and real-time monitoring.