Standing wave assisted acoustic droplet vaporization for dual payload release from acoustically responsive scaffolds

Ultrasound standing waves have been utilized for many biomedical applications. Here, we demonstrate how standing waves can enhance drug release using acoustic droplet vaporization (ADV), which is the phase-transitioning of perfluorocarbon (PFC) emulsions via ultrasound. These experiments utilized acoustically-responsive scaffolds (ARSs), which are composite fibrin hydrogels containing payload-carrying, monodispersed PFC emulsions. Single- and bi-layer ARSs were generated with dextran-loaded emulsions (diameter: 6 mm) containing either perfluorohexane, or perfluorooctane in each layer. First, we studied the influence of standing waves on payload release from single-layer ARSs. At 4 MPa peak rarefactional pressure, elevated amplitudes due to constructive superposition in the standing wave field enhanced payload release up to 35% at 2.5 MHz in a seven-day longitudinal study. Second, the effect of standing waves was combined with the frequency-dependent ADV to enhance dual payload release from bi-layer ARSs. We demonstrated the sequential release of two dextran payloads from ARSs, which were, respectively, contained within each emulsion, using temporally staggered ADV at 3 MHz (day 0) and 8.8 MHz (day 4). These results will also be discussed in the context of practical strategies for achieving similar conditions for in vivo applications