Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation

Stimulus-responsive drug delivery nanotechnologies promise noninvasive activation of the right drug at the right place at the right time. However, these systems often incorporate non-validated pharmaceutical excipients and other features that limit their clinical translation. Here we engineer the responsiveness of liposomes to a pulsed, low-intensity ultrasound activating stimulus by incorporating a generally regarded as safe excipient that alters the acoustic properties of the liposome core medium. We show that this approach permits loading and ultrasound-induced release of four drugs in vitro. We then leverage this performance to enable drug-mediated noninvasive neuromodulation of each of the central and the peripheral nervous system in vivo. These acoustically activatable liposomes formulated with common and validated pharmaceutical excipients and production processes provide a versatile system for stimulus-responsive site-targeted drug delivery and noninvasive neuromodulation, with high clinical translation potential.