Effect of Lipid Composition and Stirring Dynamics on Oxygen Microbubble Stability and Oxygen Release

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.