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

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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.