Ultrasound-triggered drug delivery: recent developments and opportunities

While ultrasound-based medical imaging is widely used in clinics, ultrasound-triggered drug delivery represents an emerging modality that takes advantage of the high tissue penetrability, general safety, and high clinical accessibility of ultrasound to solve key challenges around localized drug delivery. In this review, we analyze emerging trends in the design of drug delivery vehicles activated using different ultrasound effects ranging from cavitation, mechanical stimulation, localized heating, reactive oxygen species generation, localized gas generation, and/or penetration enhancement. In particular, we focus on vehicle designs that enable delayed burst release, sustained release, and pulsatile on-off release of drugs locally at the targeted ultrasound site, each of which has direct applications for treating specific diseases. Vehicles in which ultrasound-mediated drug release kinetics control is synergistically coupled with other therapeutic benefits of ultrasound are highlighted. Finally, we discuss key barriers to the practical translation of ultrasound-triggered drug delivery vehicles into the clinic, aiming to motivate the design of scalable and reproducible ultrasound-triggered drug delivery vehicles that can have real-world patient impact.