Manufacture of Concentrated, Lipid-based Oxygen Microbubble Emulsions by High Shear Homogenization and Serial Concentration

Manufacture of Concentrated, Lipid-based Oxygen Microbubble Emulsions by High Shear Homogenization and Serial Concentration
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DOI:
10.3791/51467
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发表时间:
2014-05-01
影响因子:
1.2
通讯作者:
Kheir, John N.
Kheir, John N.
中科院分区:
综合性期刊4区
文献类型:
--
作者:
Thomson, Lindsay M.;Polizzotti, Brian D.;Kheir, John N.

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充气微泡已发展成为超声造影剂和药物输送剂。微气泡可以通过使用超声波、机械搅拌、微流体装置或均质处理表面活性剂来产生。最近,基于脂质的氧气微泡(LOMs)被设计用于在医疗紧急情况下静脉输送氧气,逆转危及生命的低氧血症,并防止随后的器官损伤、心脏骤停和死亡。我们提出的方法,大规模生产的高氧微泡使用闭环高剪切均质机。该工艺可在90分钟内产生2 L的浓缩LOMs(体积比90%)。所得气泡的平均直径约为2 μ m,其流变学特征与血液稀释至60%体积时的流变学特征一致。该技术生产的LOMs容量大,氧纯度高,这表明该技术可能对转化研究实验室有用。
Gas-filled microbubbles have been developed as ultrasound contrast and drug delivery agents. Microbubbles can be produced by processing surfactants using sonication, mechanical agitation, microfluidic devices, or homogenization. Recently, lipid-based oxygen microbubbles (LOMs) have been designed to deliver oxygen intravenously during medical emergencies, reversing life-threatening hypoxemia, and preventing subsequent organ injury, cardiac arrest, and death. We present methods for scaled-up production of highly oxygenated microbubbles using a closed-loop high-shear homogenizer. The process can produce 2 L of concentrated LOMs (90% by volume) in 90 min. Resulting bubbles have a mean diameter of similar to 2 mu m, and a rheologic profile consistent with that of blood when diluted to 60 volume %. This technique produces LOMs in high capacity and with high oxygen purity, suggesting that this technique may be useful for translational research labs.