The release of thrombin, using acoustic droplet vaporization (ADV), from perfluoropentane double emulsions

Acoustic droplet vaporization (ADV), a process whereby liquid droplets are vaporized into gas bubbles using ultrasound, has been studied in vivo as a method to generate vascular occlusion. This work focuses on the development of a double emulsion that releases a chemical embolic agent, thrombin, upon ADV thereby potentially extending the duration of ADV-induced occlusion. Micron-sized, double emulsions were formulated, using a two-step process, with the following structure: water-in-perfluoropentane-in-water (W₁/PFP/W₂). Thrombin was contained in the W₁ phase. Emulsions produced using low shear techniques during the second emulsification step yielded the highest thrombin encapsulation (>; 95%). The ability of ADV to release the thrombin was tested by exposing the emulsions to acoustic pulses from a 3.5 MHz single-element transducer (4.7 MPa peak rarefactional pressure) while in an OptiCell™ chamber. ADV caused the activated clotting time (ACT) of citrated blood to decrease, in a statistically significant manner (p <; 0.01), compared to blood incubated with emulsions not exposed to ultrasound.