Physics of Fluids Group, Technical Medical (TechMed) Center, University of Twente, Enschede, The Netherlands.
BIOS/Lab on a Chip Group, Max Planck Center Twente for Complex Fluid Dynamics, MESA+ Institute for Nanotechnology, University of Twente, Enschede, The Netherlands.
Ultrasound Med Biol. 2024 Aug;50(8):1099-1107. doi: 10.1016/j.ultrasmedbio.2024.03.011. Epub 2024 Jun 8.
Ultrasound-triggered bubble-mediated local drug delivery has shown potential to increase therapeutic efficacy and reduce systemic side effects, by loading drugs into the microbubble shell and triggering delivery of the payload on demand using ultrasound. Understanding the behavior of the microbubbles in response to ultrasound is crucial for efficient and controlled release.
In this work, the response of microbubbles with a coating consisting of poly(2-ethyl-butyl cyanoacrylate) (PEBCA) nanoparticles and denatured casein was characterized. High-speed recordings were taken of single microbubbles, in both bright field and fluorescence.
The nanoparticle-loaded microbubbles show resonance behavior, but with a large variation in response, revealing a substantial interbubble variation in mechanical shell properties. The probability of shell rupture and the probability of nanoparticle release were found to strongly depend on microbubble size, and the most effective size was inversely proportional to the driving frequency. The probabilities of both rupture and release increased with increasing driving pressure amplitude. Rupture of the microbubble shell occurred after fewer cycles of ultrasound as the driving pressure amplitude or driving frequency was increased.
The results highlight the importance of careful selection of the driving frequency, driving pressure amplitude and duration of ultrasound to achieve the most efficient ultrasound-triggered shell rupture and nanoparticle release of protein-and-nanoparticle-stabilized microbubbles.
超声触发的气泡介导局部药物输送通过将药物加载到微泡壳中，并使用超声按需触发载药的释放，显示出增加治疗效果和减少全身副作用的潜力。了解微泡对超声的响应行为对于高效和控制释放至关重要。
在这项工作中，研究了由聚（2-乙基-丁基氰基丙烯酸酯）（PEBCA）纳米粒子和变性酪蛋白组成的涂层的微泡的响应。对单个微泡进行了高速记录，包括明场和荧光记录。
载有纳米粒子的微泡表现出共振行为，但响应变化很大，这表明机械壳性能在微泡之间存在很大差异。壳破裂的概率和纳米粒子释放的概率被发现强烈依赖于微泡的大小，而最有效的大小与驱动频率成反比。破裂和释放的概率都随着驱动压力振幅的增加而增加。随着驱动压力振幅或驱动频率的增加，微泡壳的破裂发生的超声循环次数减少。
结果强调了仔细选择驱动频率、驱动压力振幅和超声持续时间的重要性，以实现最有效的超声触发的壳破裂和蛋白质-纳米粒子稳定的微泡的纳米粒子释放。
