Novel ultrasound contrast agent based on microbubbles generated from surfactant mixtures of Span 60 and polyoxyethylene 40 stearate
Novel ultrasound contrast agent based on microbubbles generated from surfactant mixtures of Span 60 and polyoxyethylene 40 stearate
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基于由 Span 60 和聚氧乙烯 40 硬脂酸酯的表面活性剂混合物产生的微泡的新型超声造影剂。
DOI：
10.1016/j.actbio.2010.03.007
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发表时间：
2010-09-01
影响因子：
9.7
通讯作者：
Liu, Jibin
中科院分区：
文献类型：
--
作者：
Xing, Zhanwen;Ke, Hengte;Liu, Jibin
本研究以山梨糖单硬脂酸酯（Span 60）和聚氧乙烯40硬脂酸酯（PEG40S）为表面活性剂，在水介质中超声制备了新型全氟碳填充微泡作为超声造影剂。PEG40S/Span 60的比例为1:9，微泡的平均直径为2.08 +/- 1.27 μ m，超过99%的微泡的平均粒径小于8 pm，表明它们的大小适合静脉注射作为超声造影剂。采用Langmuir-Blodgett技术研究了微气泡的稳定机制，包括测量表面压力-面积（pi-A）等温线和压缩-减压循环，并在Span 60和PEG40S的二维单层上进行了测试。混合单层膜的pi-A等温线中PEG4OS摩尔分数的依赖性为两种微泡形成材料之间的相互作用提供了强有力的证据。结果表明：低表面张力的单层壳通过表面张力的降低阻碍了微泡的溶解，而表面张力的降低会产生与拉普拉斯压力相反的机械表面压力；(2)单层外壳的存在对气体从核心逸出进入水介质具有重要的屏障；(3)包封弹性稳定微泡，防止扩散驱动溶解，并解释了微泡造影剂的长保质期。初步的体内超声成像研究表明，这种稳定的微泡在灰度脉冲反演谐波成像和功率多普勒成像下表现出良好的增强效果。(C) 2010材料学报Elsevier Ltd.出版。版权所有。
In this study, novel perfluorocarbon-filled microbubbles as ultrasound contrast agent were fabricated using ultrasonication of a surfactant mixture of sorbitan monostearate (Span 60) and polyoxyethylene 40 stearate (PEG40S) in aqueous media. The microbubbles generated from a 1:9 mixture of PEG40S/Span 60 exhibited an average diameter of 2.08 +/- 1.27 mu m. More than 99% of the microbubbles had a mean particle diameter less than 8 pm, indicating that they were appropriately sized for intravenous administration as ultrasound contrast agent. The stabilization mechanism of the microbubbles was investigated by the Langmuir-Blodgett technique including the measurements of surface pressure-area (pi-A) isotherms and compression-decompression cycles with a two-dimensional monolayer of Span 60 and PEG40S. The dependence on molar fraction of PEG4OS in pi-A isotherms of mixed monolayers provided a strong evidence of interactions between the two microbubble-forming materials. It is suggested that the monolayer shell imparts good stability to the microbubbles by three means: (1) a low surface tension monolayer hinders dissolution through the reduction of surface tension, which introduces a mechanical surface pressure that counters the Laplace pressure; (2) the presence of a monolayer shell imparts a significant barrier to gas escaping from the core into the aqueous medium; and (3) encapsulation elasticity stabilizes microbubbles against diffusion-driven dissolution and explains the long shelf-life of microbubble contrast agent. The preliminary in vivo ultrasound imaging study showed that such stabilized microbubbles demonstrated excellent enhancement under grey-scale pulse inversion harmonic imaging and power Doppler imaging. (C) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.