Department of Physics and Astronomy, University of New Mexico, Albuquerque, New Mexico 87131, USA.
Langmuir. 2013 Apr 9;29(14):4485-91. doi: 10.1021/la400536e. Epub 2013 Mar 26.
Lipid-coated microbubbles and emulsions are of interest as possible ultrasound-mediated drug delivery vehicles and for their interesting behaviors and fundamental properties. We and others have noted that bubbles coated with the long chain saturated phospholipid distearoylphosphatidylcholine (DSPC) rapidly shrink to a quasistable size when repeatedly insonated with short ultrasound pulses; such stability may adversely affect the bubble's subsequent ability to deliver its pharmacological cargo. Bubbles coated with the unsaturated lipid dioleoylphosphatidylcholine (DOPC) did not show stability but did undergo an abrupt change from rapid initial shrinkage to a slow persistent shrinkage, leading ultimately to dissolution or dispersion. As DOPC and DSPC differ not only in chain saturation but also phase behavior, we performed additional studies using dimyristoyl PC (DMPC) as a coat lipid and controlled the solution temperature to study bubble behavior on exposure to repeated ultrasound pulses for the same coat, in both fluid and gel phases. We find, first, that essentially all bubbles show an initially rapid shrinkage, in which gas loss exceeds the limit imposed by gas diffusion into the surrounding medium; this rapid shrinkage may be evidence of nanoscopic bubble fragmentation. Second, upon reaching a fraction of their initial size, bubbles begin a slower shrinkage with a shrinkage rate that depends on the resting phase state of the coat lipid: fluid DMPC monolayers give a more rapid shrinkage than gel phase. DOPC-coated bubbles showed no temperature-dependent responses in the same temperature range. The results are especially interesting in that bubble compression during the pulse is likely to adiabatically heat the bubble and fluidize the coat, regardless of its initial phase state; thus, some structural feature of the resting coat, such as defect lines in the gel phase, may be important in the subsequent response to the ~3 μs ultrasound pulse.
脂质包覆的微泡和乳液作为可能的超声介导药物传递载体，以及它们有趣的行为和基本性质而受到关注。我们和其他人注意到，用长链饱和磷脂酰二硬脂酰基磷脂酰胆碱（DSPC）包覆的气泡在反复用短超声脉冲照射时会迅速收缩到准稳定大小；这种稳定性可能会不利地影响气泡随后传递其药理货物的能力。用不饱和脂质二油酰基磷脂酰胆碱（DOPC）包覆的气泡没有显示出稳定性，但确实经历了从快速初始收缩到缓慢持续收缩的突然变化，最终导致溶解或分散。由于 DOPC 和 DSPC 不仅在链饱和度上而且在相行为上有所不同，我们使用二肉豆蔻酰基 PC（DMPC）作为包覆脂质，并控制溶液温度，以研究相同包覆脂质在暴露于重复超声脉冲时的气泡行为，无论是在流体相还是凝胶相中。我们首先发现，基本上所有气泡都表现出最初的快速收缩，其中气体损失超过气体扩散到周围介质所施加的限制；这种快速收缩可能是纳米级气泡碎裂的证据。其次，在达到初始尺寸的一部分后，气泡开始以与包覆脂质的静止相状态有关的较慢收缩率进行收缩：流体 DMPC 单层比凝胶相具有更快的收缩率。在相同温度范围内，DOPC 包覆的气泡没有表现出温度依赖性响应。这些结果特别有趣，因为在脉冲期间气泡的压缩可能会使气泡绝热加热并使包膜流化，无论其初始相状态如何；因此，静止包膜的某些结构特征，例如凝胶相中的缺陷线，可能对随后对~3 μs 超声脉冲的响应很重要。
