Kakiuchi Kenta, Borden Mark Andrew
Biomedical Engineering Program, University of Colorado Boulder, Boulder, Colorado 80309, United States.
Mechanical Engineering Department, University of Colorado Boulder, Boulder, Colorado 80309, United States.
Langmuir. 2025 Jan 28;41(3):1745-1755. doi: 10.1021/acs.langmuir.4c04104. Epub 2025 Jan 15.
Lipid-coated oxygen microbubbles (OMBs) are being investigated for biomedical applications to alleviate hypoxia such as systemic oxygenation and image-guided radiosensitization therapy. Additionally, they hold potential for boarder application as oxygen carriers beyond the biomedical filed. Understanding the stability and oxygen release properties of OMBs in dynamic aqueous environments is critical for these applications. In this study, we found that OMBs composed of longer acyl chain phospholipids (DSPC and DBPC) were stable in storage for at least 1 week, unlike the shorter acyl chain phospholipid (DPPC). OMBs were also more stable with a diacyl PEG-PE emulsifier compared with single-chain PEG-40 stearate. Dilution of OMBs did not alter the average diameter. While previous studies have examined the theoretical and experimental aspects of oxygen release from OMBs under static conditions, quantitative evaluations of OMB dispersions under dynamic stirring conditions remain limited. Here, we introduce a novel oxygen measurement method that quantitatively tracks the transition of the dissolved oxygen concentration in an aqueous medium upon mixing with a bolus of OMBs. Our results indicate that a 50 vol % OMB dispersion releases more than 330 mg/L of oxygen, surpassing arterial oxygen levels, and that more than 95% of this oxygen is released within 30 s. The rate of oxygenation of the OMB dispersions was comparable to that of a bolus injection of oxygen-saturated water under sufficient agitation, indicating that convection in the aqueous medium is the limiting transport mechanism. However, the lipid shell had a measurable effect on the oxygen release rate, which correlated with its oxygen permeability. Increasing the stirring speed increased both oxygen release rate and total amount of oxygen released. Overall, this study elucidates the fundamental stability and mass transport properties of the OMB dispersions under practical stirring conditions.
脂质包被的氧微泡（OMBs）正被研究用于生物医学应用，以缓解缺氧，如全身氧合和图像引导的放射增敏治疗。此外，它们作为氧载体在生物医学领域之外还有更广泛的应用潜力。了解OMBs在动态水性环境中的稳定性和氧释放特性对于这些应用至关重要。在本研究中，我们发现由较长酰基链磷脂（DSPC和DBPC）组成的OMBs在储存时至少1周内是稳定的，这与较短酰基链磷脂（DPPC）不同。与单链PEG - 40硬脂酸酯相比，含有二酰基PEG - PE乳化剂的OMBs也更稳定。OMBs的稀释不会改变平均直径。虽然先前的研究已经考察了静态条件下OMBs氧释放的理论和实验方面，但在动态搅拌条件下对OMB分散体的定量评估仍然有限。在这里，我们介绍一种新颖的氧测量方法，该方法可以定量跟踪与一大团OMBs混合后水性介质中溶解氧浓度的变化。我们的结果表明，50体积%的OMB分散体释放的氧气超过330毫克/升，超过动脉氧水平，并且其中超过95%的氧气在30秒内释放。在充分搅拌下，OMB分散体的氧合速率与注射含饱和氧水团注的速率相当，这表明水性介质中的对流是限制传输机制。然而，脂质壳对氧释放速率有可测量的影响，这与其氧渗透性相关。提高搅拌速度会增加氧释放速率和释放的氧气总量。总体而言，本研究阐明了实际搅拌条件下OMB分散体的基本稳定性和传质特性。
