Corked Microcapsules\nEnabling Controlled Ultrasound-Mediated\nProtein Delivery

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