A review on piezoelectric-triggered materials for on-demand drug delivery: Mechanisms, materials, and translational perspectives

Objectives Conventional drug delivery systems offer limited real-time control over dosing, localization, and responsiveness to dynamic biological environments. This review aims to establish a unified mechanistic framework for piezoelectric-triggered drug delivery systems (DDSs), clearly distinguishing intrinsic piezoelectric drug carriers, piezocatalytic systems, magnetoelectric systems, and piezoelectric device-assisted delivery systems, a distinction often blurred in prior reviews, and to provide a quantitative, comparative synthesis of activation modalities, materials, and release mechanisms. Methods A master dataset was manually compiled from 43 study entries included in this review. Analysis-specific subsets were then selected according to the availability of extractable information required for each visualization and comparison. For example, the Sankey diagram included 37 studies with sufficient information to map therapeutic application, activation trigger, release mechanism, and material platform, while the drug-distribution analysis included 40 studies with relevant therapeutic-agent information. Results Activation modalities (ultrasound, mechanical loading, magnetic coupling, electrical stimulation) were linked to distinct release mechanisms, bond cleavage, matrix swelling/degradation, electrostatic disruption, carrier reorganization, magnetoelectric coupling, and electroporation-assisted uptake, across inorganic ceramic, polymeric, biomolecular, and hybrid material classes. Representative case studies demonstrated substantial gains in drug release efficiency, intracellular transport, immune modulation, and tumor inhibition, though quantitative reporting of piezoelectric and stimulation parameters remained inconsistent across the literature. Conclusions Piezoelectric DDSs offer a mechanistically distinct route to wireless, on-demand, spatiotemporally precise drug release, but clinical translation is constrained by inconsistent characterization, insufficient long-term biosafety data, and regulatory ambiguity for hybrid device–drug products. Standardized reporting, rigorous control experiments, and biodegradable material development are proposed as design priorities for future clinically viable platforms.