Abstract
The new ultrasound drug carrier, phase-change droplet (PCD), with liquid perfluorocarbon in lipid shell, and steady in the circulation, was proposed by R. E. Apfel in 1998. PCDs were promising for local drug delivery due to their ability to undergo acoustic droplet vaporization (ADV) under ultrasound excitations. However, no study has investigated the transient dynamics of drug release, since ADV occurred on microsecond scale and drugs were hardly identified in conventional bright field microscopy. Here, we established a high-speed fluorescence imaging system to visualize the process of drug release during ADV. The aim of the study was to find out the way of drug release from PCDs, the distribution of the released drug, the effect between acoustic parameters and release number, and finally the mechanism of drug release from PCDs. Drug release from PCDs must be triggered by acoustic parameter higher than specific level (at least 9 MPa). At the pressures higher than ADV threshold, the shedding drug were observed only on contacted wall between droplets and tube. To figure out the mechanism of drug release from PCDs, the process was captured by high-speed fluorescence imaging system. From quantified images, acoustic pressure had effect on lipid dynamic on bubble shell, which was resulted from directionally converging flow. Moreover, the bright-field images were quantified to verify the effects of the evolution of bubble resulting in converging flow. In summary, the mechanism of drug release from PCDs was that ADV triggered the evolution of bubble, which resulting in converging flow. The flow induced the effect of lipid bending and shedding with drugs. Finally, small PCDs or high pressure induced the high efficiency on either release number or release distance. Through high-speed images, it was proved that the release efficiency was related to evolution of bubble.