Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation
Mahaveer P. Purohit, Brenda Yu, Kanchan Sinha Roy, Yun Xiang, Sedona N. Ewbank, Matine Azadian, Alex R. Hart, Gabriella P. B. Muwanga, Payton Martinez, Jeffrey B. Wang, Ali K. Taoube, Eric Markarian, Nicholas Macedo, Audrey K. Kwan, Diego Gómez López, Raag D. Airan
Abstract
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. Acoustically activatable nanocarriers made by incorporating 5% sucrose into liposomes release drug with low-intensity ultrasound, providing a readily clinically translatable system for both central and peripheral noninvasive neuromodulation.