Department of Radiology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106-7207, USA.
Small. 2022 Jun;18(24):e2200810. doi: 10.1002/smll.202200810. Epub 2022 May 19.
Shell-stabilized gas microbubbles (MB) and nanobubbles (NB) are frequently used for biomedical ultrasound imaging and therapeutic applications. While it is widely recognized that monodisperse bubbles can be more effective in these applications, the efficient formulation of uniform bubbles at high concentrations is difficult to achieve. Here, it is demonstrated that a standard mini-extruder setup, commonly used to make vesicles or liposomes, can be used to quickly and efficiently generate monodisperse NBs with high yield. In this highly reproducible technique, the NBs obtained have an average diameter of 0.16 ± 0.05 µm and concentration of 6.2 ± 1.8 × 10 NBs mL compared to 0.32 ± 0.1 µm and 3.2 ± 0.7 × 10 mL for NBs made using mechanical agitation. Parameters affecting the extrusion and NB generation process including the temperature, concentration of the lipid solution, and the number of passages through the extruder are also examined. Moreover, it is demonstrated that extruded NBs show a strong acoustic response in vitro and a strong and persistent US signal enhancement under nonlinear contrast enhanced ultrasound imaging in mice. The extrusion process is a new, efficient, and scalable technique that can be used to easily produce high yield smaller monodispersed nanobubbles.
壳稳定的气体微泡（MB）和纳米泡（NB）常用于生物医学超声成像和治疗应用。虽然人们普遍认为单分散泡在这些应用中更有效，但很难在高浓度下高效地形成均匀的泡。本文证明了一种标准的微型挤出器装置，通常用于制备囊泡或脂质体，可用于快速有效地生成高产率的单分散纳米泡。在这种高度重现性的技术中，得到的纳米泡的平均直径为 0.16 ± 0.05 μm，浓度为 6.2 ± 1.8 × 10 个纳米泡/mL，而使用机械搅拌得到的纳米泡的平均直径为 0.32 ± 0.1 μm，浓度为 3.2 ± 0.7 × 10 个纳米泡/mL。还研究了影响挤出和纳米泡生成过程的参数，包括温度、脂质溶液的浓度和通过挤出机的次数。此外，还证明了挤出的纳米泡在体外具有很强的声学响应，并且在小鼠的非线性对比增强超声成像下具有很强且持久的 US 信号增强。该挤出工艺是一种新的、高效的、可扩展的技术，可用于轻松生产高产率的小单分散纳米泡。
