We have developed oxygen filled microbubbles, SE61_O2, for localized, ultrasound-triggered oxygen delivery to hypoxic tumors prior to radiation therapy. Microbubbles, created by sonication, have a shell composed of D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and sorbitan monostearate. Preliminary studies in mice with breast tumor xenographs showed that increases in oxygen partial pressure levels lasted less than 3 min, which is insufficient for most clinical applications. Hence, we investigated the potential of incorporating a hydrophobic antiglycolytic drug, modeled with Nile red. A new fabrication method was developed by first creating drug-loaded TPGS micelles. The resulting microbubbles had similar shell compositions, physical size, morphology, and acoustic properties as the original method. However, microbubble yield was more than doubled, resulting in twice the encapsulation efficiency. For the TPGS micelle method these include similar shell compositions (94.4 ± 0.6 % Montane 60), physical size post freeze-drying and reconstitution (1.57 ± 0.42 μm), morphology (spherical), and acoustic properties (maximum enhancement 19.92 ± 0.55 dB). However, microbubble yield was more than doubled, resulting in twice the encapsulation efficiency (up to 10.49 %). We propose that a nonideal mixture is formed when the surfactants are combined by the standard method, resulting in the formation of mixed micelles that are more stable, making microbubble creation more difficult during the sonication step.

我们开发了充满氧气的微气泡，SE61 _O2，用于在放射治疗之前将局部超声触发的氧气输送到缺氧肿瘤。通过超声处理产生的微泡具有由 D-α-生育酚聚乙二醇 1000 琥珀酸酯 (TPGS) 和脱水山梨糖醇单硬脂酸酯组成的外壳。对具有乳腺肿瘤异种移植物的小鼠进行的初步研究表明，氧分压水平的增加持续不到 3 分钟，这对于大多数临床应用来说是不够的。因此，我们研究了加入疏水性抗糖酵解药物的潜力，以尼罗红为模型。通过首先创建载药 TPGS 胶束开发了一种新的制造方法。由此产生的微泡具有与原始方法相似的壳组成、物理尺寸、形态和声学特性。然而，微泡产量增加了一倍多，导致两倍的封装效率。对于 TPGS 胶束方法，这些包括相似的壳成分（94.4 ± 0.6 % Montane 60）、冷冻干燥和重建后的物理尺寸（1.57 ± 0.42 μm）、形态（球形）和声学特性（最大增强 19.92 ± 0.55 dB） . 然而，微泡产量增加了一倍以上，导致封装效率增加一倍（高达 10.49%）。我们提出当表面活性剂通过标准方法结合时会形成非理想混合物，从而导致形成更稳定的混合胶束，从而使在超声处理步骤中更难产生微泡。和声学特性（最大增强 19.92 ± 0.55 dB）。然而，微泡产量增加了一倍以上，导致封装效率增加一倍（高达 10.49%）。我们提出当表面活性剂通过标准方法结合时会形成非理想混合物，从而导致形成更稳定的混合胶束，从而使在超声处理步骤中更难产生微泡。和声学特性（最大增强 19.92 ± 0.55 dB）。然而，微泡产量增加了一倍以上，导致封装效率增加一倍（高达 10.49%）。我们提出当表面活性剂通过标准方法结合时会形成非理想混合物，从而导致形成更稳定的混合胶束，从而使在超声处理步骤中更难产生微泡。