University of Duisburg-Essen, Institute of Physiology, University Hospital Essen, Hufelandstraße 55, 45122 Essen, Germany.
Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, bygning 1116, 8000 Aarhus C, Denmark.
Langmuir. 2022 Aug 30;38(34):10351-10361. doi: 10.1021/acs.langmuir.1c03388. Epub 2022 Aug 15.
This work aimed at the development of a stable albumin-perfluorocarbon (o/w) emulsion as an artificial oxygen carrier suitable for clinical application. So far, albumin-perfluorocarbon-(o/w) emulsions have been successfully applied in preclinical trials. Cross-linking a variety of different physical and chemical methods for the characterization of an albumin-perfluorocarbon (PFC)-(o/w) emulsion was necessary to gain a deep understanding of its specific emulsification processes during high-pressure homogenization. High-pressure homogenization is simple but incorporates complex physical reactions, with many factors influencing the formation of PFC droplets and their coating. This work describes and interprets the impact of albumin concentration, homogenization pressure, and repeated microfluidizer passages on PFC-droplet formation; its influence on storage stability; and the overcoming of obstacles in preparing stable nanoemulsions. The applied methods comprise dynamic light scattering, static light scattering, cryo- and non-cryo-scanning and transmission electron microscopies, nuclear magnetic resonance spectroscopy, light microscopy, amperometric oxygen measurements, and biochemical methods. The use of this wide range of methods provided a sufficiently comprehensive picture of this polydisperse emulsion. Optimization of PFC-droplet formation by means of temperature and pressure gradients results in an emulsion with improved storage stability (tested up to 5 months) that possibly qualifies for clinical applications. Adaptations in the manufacturing process strikingly changed the physical properties of the emulsion but did not affect its oxygen capacity.
本研究旨在开发一种稳定的白蛋白-全氟碳（o/w）乳剂作为一种适合临床应用的人工氧载体。迄今为止，白蛋白-全氟碳（o/w）乳剂已成功应用于临床前研究。为了深入了解其在高压匀质过程中的特定乳化过程，需要对各种不同的物理和化学交联方法进行表征。
高压匀质虽然简单，但包含复杂的物理反应，许多因素影响 PFC 液滴的形成及其包覆。本工作描述并解释了白蛋白浓度、匀质压力和重复微射流处理对 PFC 液滴形成的影响；对储存稳定性的影响；以及克服制备稳定纳米乳剂的障碍。应用的方法包括动态光散射、静态光散射、冷冻和非冷冻扫描和透射电子显微镜、核磁共振波谱、光显微镜、电流测定氧测量和生化方法。这种广泛的方法应用提供了这种多分散乳液的足够全面的图片。通过温度和压力梯度优化 PFC 液滴的形成，可得到储存稳定性提高的乳液（测试长达 5 个月），可能有资格用于临床应用。
在制造过程中的适应性变化显著改变了乳液的物理性质，但不影响其氧容量。
