Controlling cavitation for controlled release

We present a novel, long-lived ultrasound contrast vehicle with triggered drug release capability. The vehicle comprises shell-stabilized microbubbles encapsulated within the aqueous core of a vesicle-like microcapsule. Encapsulating microbubbles enhances their longevity as ultrasound contrast agents by shielding the microbubbles from dissolution in a bulk aqueous phase. Moreover, co-encapsulation of microbubbles with a drug offers a simple mechanism for controlled drug release; ultrasound-induced cavitation of the microbubbles within microcapsules causes leakage of the inner contents from the microcapsules into the surrounding medium. By controlling the extent of microbubble cavitation one can control when - and at what rate - the microcapsule releases drug. Here we describe construction of the vehicle, how one can tune the microbubble cavitation threshold via changes in microbubble shell elasticity, and how ultrasound-induced leakage varies with microcapsule shell type and composition. We show results for different microcapsule shell materials, including self-assembled bilayers of phospholipids (liposomes) and di-block copolymers (polymersomes) and a non-self-assembled, macromolecular polymer, using the fluorescent dye calcein as a drug mimic.