Department of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway; Department of Physics, Norwegian University of Science and Technology, Trondheim, Norway; Neoety AS, Kløfta, Norway.
Department of Clinical Science, University of Bergen, Bergen, Norway.
Ultrason Sonochem. 2022 Apr;85:105986. doi: 10.1016/j.ultsonch.2022.105986. Epub 2022 Mar 23.
The aim of this study was to develop high load-capacity antibubbles that can be visualized using diagnostic ultrasound and the encapsulated drug can be released and delivered using clinically translatable ultrasound. The antibubbles were developed by optimising a silica nanoparticle stabilised double emulsion template. We produced an emulsion with a mean size diameter of 4.23 ± 1.63 µm where 38.9 ± 3.1% of the droplets contained a one or more cores. Following conversion to antibubbles, the mean size decreased to 2.96 ± 1.94 µm where 99% of antibubbles were <10 µm. The antibubbles had a peak attenuation of 4.8 dB/cm at 3.0 MHz at a concentration of 200 × 10 particles/mL and showed distinct attenuation spikes at frequencies between 5.5 and 13.5 MHz. No increase in subharmonic response was observed for the antibubbles in contrast to SonoVue®. High-speed imaging revealed that antibubbles can release their cores at MIs of 0.6. In vivo imaging indicated that the antibubbles have a long half-life of 68.49 s vs. 40.02 s for SonoVue®. The antibubbles could be visualised using diagnostic ultrasound and could be disrupted at MIs of ≥0.6. The in vitro drug delivery results showed that antibubbles can significantly improve drug delivery (p < 0.0001) and deliver the drug within the antibubbles. In conclusion antibubbles are a viable concept for ultrasound guided drug delivery.
本研究旨在开发高载药量的抗气泡，使其可通过诊断超声可视化，并可使用临床转化的超声释放和传递包裹的药物。抗气泡是通过优化二氧化硅纳米颗粒稳定的双重乳液模板来开发的。我们制得了平均直径为 4.23 ± 1.63 μm 的乳液，其中 38.9 ± 3.1%的液滴含有一个或多个核心。转化为抗气泡后，平均直径减小至 2.96 ± 1.94 μm，其中 99%的抗气泡小于 10 μm。抗气泡在浓度为 200×10 个/毫升时在 3.0 MHz 处的峰值衰减为 4.8 dB/cm，在 5.5 至 13.5 MHz 之间的频率处显示出明显的衰减峰值。与 SonoVue®相比，抗气泡未观察到亚谐波响应增加。高速成像显示，抗气泡可以在 MI 为 0.6 时释放其核心。体内成像表明，抗气泡的半衰期为 68.49 s，而 SonoVue®的半衰期为 40.02 s。抗气泡可通过诊断超声进行可视化，并可在 MI 大于等于 0.6 时破坏。体外药物递送结果表明，抗气泡可显著提高药物递送效率（p<0.0001）并在抗气泡内递送药物。总之，抗气泡是超声引导药物递送的一种可行方案。
