High-speed fluorescence imaging of ultrasound-triggered drug release from phase-change droplets

Phase-change droplets are promising for drug delivery due to the ability to undergo acoustic droplet vaporization (ADV) under ultrasound exposure. No study has investigated the distribution dynamics of drug-surfactant complex, since ADV is a rapid process hardly observed with conventional microscopy or spectroscopy. Here we established a high-speed fluorescence microscopy system to visualize the drug distribution dynamics during the ADV of DiI-loaded perfluoropentane droplets with sizes of 3-7 μm at capture rates of up to 100 kfps. The results show that the DiI-lipid complexes tended to remain on the bubble surface showing a heterogeneous pattern when ADV occurred at the low acoustic pressures (close to the ADV thresholds). However, at the pressures much higher than ADV threshold, the shedding of DiI-lipid complexes were observed for droplets only on the sides they contacted the tube wall. The pressure and spatial dependence means additional mechanical forces aside from the outward expansion force arising from ADV were exerted to shed DiI-lipid complexes off the bubble surface to self-assemble into vesicles. The near-wall preference of vesicle release means that ADV may be a useful technique in controlled drug delivery applications especially in the vascular targeting scenario. This study provides valuable information for the optimization of ADV-based drug delivery.