Ultrasound-triggered disruption of microbubbles in drug delivery systems (DDS) is a promising technique for reducing side effects. Despite its potential efficacy in reducing side effects, the disruption ratio of the microbubble population remains poorly understood. In this study, we experimentally investigated the effects of diameter distribution and particle number concentration (PNC) of the microbubbles on their disruption ratio by quantifying the number of disrupted bubbles after ultrasonic irradiation. The experiments were conducted using polymer-shelled microbubbles suspended in a gelatin-filled microchamber and exposed to focused ultrasound at 1 MHz with 30 cycles. The size of microbubbles was sorted by filtration, and the concentration within the microchamber was determined by image processing. The disruption ratio of each microbubble population was evaluated as a function of PNC. The sorted microbubble population with resonant size exhibited a significantly greater disruption ratio, exceeding that of polydisperse populations by more than twofold. Moreover, the results showed an exponential decrease in the disruption ratio with increasing PNC, accompanied by a monotonic increase in the number of intact microbubbles. This suggests an increased risk of side effects even in the resonant-sized microbubble population at high PNC. Conversely, in the low PNC region, where the disruption ratio is higher, the lower number of disrupted microbubbles may lead to prolonging the treatment time. These findings highlight the necessity of determining an appropriate PNC by considering both treatment time and the risk of side effects.
Kanashima et al. (Wed,) studied this question.