Driving Drugs Deeper: Force‐Driven Microneedle Systems for Active Therapy and Their Road Towards Clinical Implementation

Vollständiger Abstract

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ABSTRACT Transdermal delivery of macromolecules and biologics is constrained by the barrier function of skin. First‐generation microneedle arrays address this issue by penetrating the stratum corneum; however, their passive, diffusion‐based release limits delivery depth, kinetics, and adaptability. In this review, we discuss force‐driven microneedles (F‐MNs) as a shift from passive permeation to active propulsion. F‐MNs integrate mechanisms that generate localized physical driving forces to rapidly and controllably drive therapeutic payloads into tissue, achieving millimeter‐scale penetration within seconds to minutes. We categorize four principal modalities based on their force‐generation mechanism: gas‐driven microneedles, cavitation‐driven microneedles, magnetically actuated microneedles, and iontophoresis‐enhanced microneedles. For each class, underlying mechanisms, material choices, safety considerations, and translational challenges are presented. We further discuss how artificial intelligence can guide F‐MNs' design, manufacturing and closed‐loop theranostic control. We also highlight the unique fabrication requirements of F‐MNs, including multi‐material integration, spatial compartmentalization of force‐generating components, stimulus‐responsive architectures, and device‐level quality control. By framing F‐MNs around their force‐generation mechanisms and translational barriers, this review outlines design rules and clinical application spaces for deep, rapid, and controllable microneedle‐mediated therapy across transdermal, mucosal, gastrointestinal, wound, and tumor‐related delivery settings.