Ultrasound-responsive hydrogel microcapsules for on-demand drug release

Abstract

Hydrogel-based implantable systems offer viable solutions for localized drug delivery but often lack the ability to easily achieve on-demand actuation or real-time tuning of release kinetics in response to physiological changes. Here, we present a hydrogel microcapsules produced using two-phase microfluidics that can release drugs on demand as triggered by focused ultrasound (FUS). The biphasic microcapsules consist of an outer phase of mixed molecular weight (MW) poly(ethylene glycol) diacrylate that mitigates premature payload release and an inner phase of high MW dextran with payload that breaks down in response to FUS. Compound release from microcapsules could be triggered as desired; 0.4 μg of payload was released across 16 on-demand steps over days. We detected broadband acoustic signals amidst low heating, suggesting inertial cavitation as a key mechanism for payload release. Overall, FUS-responsive microcapsules are a biocompatible and wirelessly triggerable structure for on-demand drug delivery over days to weeks.