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

合作研究：含气泡脂质体水核中的声学微流，通过剪切诱导的双层重组控制释放

• 批准号: 1602884
• 负责人: Kausik Sarkar
• 金额: $ 22.77万
• 依托单位: George Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1602884&HistoricalAwards=false
• 关键词: Collaborative; Research; Acoustic; micro; streaming

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.

PI：WRENN，Steven / Sarkar，Kausikpropopals编号：1603007 /1602884拟议的研究集中于研究液滴体内微泡的行为。当用脂质涂覆时，微泡会变得稳定，然后嵌套在充满水的细胞中。这种布置可以具有具有生物学兴趣的应用，例如通过对气泡的声学反应进行成像，例如药物输送技术和诊断。涂层微泡已经可用于对比度增强超声成像。将它们嵌套在带有囊泡的药物中的巨大潜力作为“疗法”的车辆，这意味着它们可用于治疗和诊断应用。同时，嵌套可以保护微泡免受气体扩散，从而增加了其寿命从几分钟到几个小时。然而，筑巢的微泡会导致微泡声活性的巨大变化和所得的流体动力学，包括声学微流动。几年前首次在实验中证明了嵌套概念，嵌套影响声学微流的机制尚不清楚。涉及嵌套微泡的实验和理论研究都很少。这是该协作建议的目的。研究团队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，同时得出计算嵌套壳的数学和计算流体动力学模型，并同意实验结果。有三个特定的目的：1）在嵌套配置中计算流线，并沿嵌套磷脂双层的内部传单计算所得的剪切应力曲线； 2）确定双层对微流的应力响应的机制； 3）量化微流的灵敏度以及对超声输入参数和化学衍生的嵌套膜性能的敏感性。拟议工作的更广泛的影响是开发可用于超声成像和/或药物输送的疗法车辆。最终应用可以是在实际临床环境中使用嵌套微泡。该提案还包括一项计划，以积极招募来自摩根州立大学的代表性不足的少数族裔学生，以及高中，本科和研究生的教育活动。