Collaborative Research: Acoustic micro-streaming in the aqueous core of bubble-containing liposomes for controlled release via shear-induced bilayer reorganization

主要研究者：Wrenn，Steven / Sarkar，Kausik提案编号：1603007 /1602884拟议的研究重点是研究液滴内微气泡的行为。当微泡被脂质包被并嵌套在充满水的细胞中时，微泡变得稳定。这种布置可以具有具有生物学兴趣的应用，例如药物递送技术和通过气泡的声学响应的成像的诊断。包被的微泡已经可用于对比增强超声成像。将它们嵌套在载药囊泡内赋予了作为“治疗诊断”载体的巨大潜力，这意味着它们可以用于治疗和诊断应用。与此同时，嵌套可以保护微泡免受气体扩散，将其寿命从几分钟延长到几小时。然而，嵌套的微泡导致微泡声学活动和由此产生的流体动力学，包括声学微流的显着变化。嵌套的概念在几年前第一次被实验证明，嵌套影响声学微流的机制还不清楚;涉及嵌套微泡的实验和理论研究都很少。这就是这次合作的目的。研究小组将对各种嵌套配方进行系统和详尽的声学和物理化学测试，同时推导出数学和计算流体动力学模型，这些模型解释了嵌套外壳并与实验结果一致。有三个具体目标：1）计算嵌套构造中的流线，并计算沿嵌套磷脂双层的内小叶沿着的所得剪切应力分布; 2）识别双层响应于微流产生的应力而自身重构的机制;和3）量化微流的敏感性和双层对超声输入参数和化学衍生的嵌套膜性质的响应。拟议工作的更广泛影响是开发一种可用于超声成像和/或药物输送的治疗诊断工具。最终应用可以是在实际临床环境中使用嵌套微泡。该提案还包括一项积极从摩根州立大学招收代表性不足的少数民族学生的计划，以及为高中、本科和研究生开展的教育活动。

PI: Wrenn, Steven / Sarkar, KausikProposal Number: 1603007 / 1602884The proposed research is focused on the study of the behavior of microbubbles inside a liquid drop. The microbubbles become stable when coated with lipids and then nested in a cell that is filled with water. This arrangement can have applications with biological interest, such as drug delivery techniques and diagnostics through imaging of the acoustic response of the bubbles. Coated microbubbles are already useful for contrast enhanced ultrasound imaging. Nesting them inside a drug bearing vesicle confers great potential as "theranostic" vehicles, meaning they can be used for both therapeutic and diagnostic applications. At the same time, nesting can protect microbubbles against gas diffusion, enhancing their life time from minutes to hours. However, nesting a microbubble leads to dramatic changes in microbubble acoustical activity and the resulting fluid dynamics, including acoustic microstreaming. The nesting concept was demonstrated experimentally for the first time just a few years ago, and the mechanism by which nesting impacts acoustic microstreaming is not yet known in detail; both experimental and theoretical studies involving nested microbubbles are scant. This is the objective of this collaborative proposal. The research team will perform a systematic and exhaustive series of acoustic and physicochemical tests of various nested formulations, while simultaneously deriving mathematical and computational fluid dynamics models that account for the nesting shell and agree with the experimental results. There are three specific aims: 1) compute the streamlines in a nested configuration and calculate the resulting shear stress profile along the inner leaflet of the nesting phospholipid bilayer; 2) identify the mechanism(s) by which the bilayer restructures itself in response to the stresses produced by microstreaming; and 3) quantify the sensitivity of microstreaming and the bilayer response to ultrasonic input parameters and chemically derived nesting membrane properties. The broader impact of the proposed work is to develop a theranostic vehicle that can be used for ultrasound imaging and/or drug delivery. The end application could be the use of nested micro-bubbles in actual clinical environments. The proposal also includes a plan to actively recruit underrepresented minority students from Morgan State, as well as educational activities for high school, undergraduate and graduate students.