Corked Microcapsules Enabling Controlled Ultrasound-Mediated Protein Delivery

While ultrasound represents a facile, portable, and noninvasive trigger for drug delivery vehicles, most reported ultrasound-triggered drug delivery vehicles predominately present "burst" release profiles that are hard to control after the initial activation stimulus. Herein, we report a submerged electrospraying technique to fabricate protein-loaded microcapsules in which silica "corks" are embedded within the microcapsule shell. Upon the application of an ultrasound trigger, the corks can be perturbed within the shell, allowing for the release of the protein payload through a phantom tissue mimic to a degree proportional to the number/time of pulses applied. Specifically, multiple ultrasound pulses were shown to enable a 15- to 23-fold increase in the rate of release of the model bovine serum albumin protein payload relative to no ultrasound being applied, with release returning to a lower level when the ultrasound stimulus was removed. Coupled with the low cytotoxicity of the vehicle components, the corked microcapsules show promise for expanding the potential to use ultrasound to facilitate both on-demand and pulsatile release profiles.