Phospholipid-coated microbubbles are ultrasound contrast agents that can be employed for ultrasound molecular imaging and drug delivery. For safe and effective implementation, microbubbles must respond uniformly and predictably to ultrasound. Therefore, we investigated how lipid handling and phase distribution affected the variability in the acoustic behavior of microbubbles. Cholesterol was used to modify the lateral molecular packing of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-based microbubbles. To assess the effect of lipid handling, microbubbles were produced by a direct method, i.e., lipids directly dispersed in an aqueous medium or indirect method, i.e., lipids first dissolved in an organic solvent. The lipid phase and ligand distribution in the microbubble coating were investigated using confocal microscopy, and the acoustic response was recorded with the Brandaris 128 ultra-high-speed camera. In microbubbles with 12 mol% cholesterol, the lipids were miscible and all in the same phase, which resulted in more buckle formation, lower shell elasticity and higher shell viscosity. Indirect DSPC microbubbles had a more uniform response to ultrasound than direct DSPC and indirect DSPC-cholesterol microbubbles. The difference in lipid handling between direct and indirect DSPC microbubbles significantly affected the acoustic behavior. Indirect DSPC microbubbles are the most promising candidate for ultrasound molecular imaging and drug delivery applications.

中文翻译：

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脂质处理和相分布对微泡声行为的影响

磷脂包被的微泡是超声造影剂，可用于超声分子成像和药物递送。为了安全有效地实施，微泡必须对超声波做出统一且可预测的响应。因此，我们研究了脂质处理和相分布如何影响微泡声行为的可变性。胆固醇被用来修饰1,2-二硬脂酰-sn的横向分子堆积-甘油-3-磷酸胆碱（DSPC）的微泡。为了评估脂质处理的效果，通过直接方法（即，将脂质直接分散在水性介质中）或间接方法（即，首先将脂质溶解在有机溶剂中）产生微泡。使用共聚焦显微镜研究了微泡涂层中的脂质相和配体分布，并使用Brandaris 128超高速相机记录了声学响应。在胆固醇含量为12 mol％的微泡中，脂质是可混溶的并且都处于同一相，这导致更多的扣环形成，较低的壳体弹性和较高的壳体粘度。间接DSPC微泡比直接DSPC和间接DSPC-胆固醇微泡对超声的响应更为均匀。直接和间接DSPC微泡之间的脂质处理差异极大地影响了声学性能。间接DSPC微泡是超声分子成像和药物输送应用中最有希望的候选者。