Mechanistic insights into ultrasound-responsive implantable drug delivery systems

Stimulus-responsive drug delivery systems have been widely explored to achieve controlled, site-specific drug release. Among various stimuli, ultrasound offers several advantages as an external trigger, including cost-effectiveness, deep tissue penetration, and precise spatiotemporal control. While hydrogel and microbubble associated systems have been extensively studied, reservoir-type implants remain underexplored despite their potential for long-term therapy. In this study, a biodegradable polymeric reservoir implant with porous rate-controlling membrane was developed, with systematically evaluated ultrasound-responsive behaviour. Biosafety was assessed through temperature monitoring, mechanical index calculations, and histological analysis, leading to the selection of 3 MHz, 3 W/cm² ultrasound for 5 min with 9.13° C increase as a safe operating condition. Under the selected setting, ultrasound significantly enhanced drug release for around 9.7-fold by accelerating drug dissolution and diffusion, without altering the structural properties of the release membrane. Collectively, these findings provide mechanistic insight into ultrasound-responsive reservoir implants and support their potential application in managing chronic conditions, where controllable, on-demand drug release is highly desirable.