Ultrasound-responsive PDMS platform for controlled and reversible drug delivery

Controlled, localized, and on-demand drug delivery systems areessential for maximizing therapeutic efficacy while minimizing off-target effects. Here, we present a polydimethylsiloxane (PDMS)-based microchip enabling reversible, ultrasound (US)-triggered release of encapsulated drugs. The platform employs low-frequency US (20 kHz) to induce cavitation, allowing repeatable activation of the polymer matrix without passive drug leakage. Using fluorescein as a model compound, we demonstrate linear zero-order release kinetics under continuous US stimulation. Furthermore, reversible on/off control of drug release was achieved for up to five cycles of pulsed US, with each cycle releasing an average of 12.7 ± 2.5% of the loaded fluorescein. Release efficiency was tunable through adjustment of US power and initial drug loading concentration, both exhibiting linear correlations with the released dose (R² = 0.87 and 0.96, respectively). Variations in PDMS stiffness did not significantly affect release behavior within the tested range (7–30 MPa), with all formulations yielding a comparable average release of 10.9 ± 0.7%, supporting adaptability across diverse tissue environments. Solvent selection during formulation had no measurable impact on release performance after curing, indicating broad compatibility with pharmaceutical manufacturing workflows. Biocompatibility was confirmed using XTT assays and immunostaining of primary cortical neurons, revealing no cytotoxicity or morphological alterations. In vitro imaging of intact mouse eyes demonstrated effective US-triggered delivery and diffusion of fluorescein across retinal layers, resulting in increased mean fluorescence intensity compared to untreated control eyes, without detectable structural damage. Functional delivery of adrenaline from the PDMS chip was further validated by multi-electrode array recordings of cortical neurons, showing significant and controlled suppression of neuronal activity. Collectively, these results establish this platform as a promising non-invasive, targeted, and patient-tailored drug delivery system, with particular relevance for ophthalmic therapy and neuromodulation, and support its further validation in in-vivo and translational studies.