Structural changes and imaging signatures of acoustically sensitive microcapsules under ultrasound

The ultrasound drug delivery field is actively designing new agents that would obviate the problems of just using microbubbles for drug delivery. Microbubbles have very short circulation time (minutes), low payload and large size (2-10μm), all of these aspects are not ideal for systemic drug delivery. However, microbubble carriers provide excellent image contrast and their use for image guidance can be exploited. In this paper, we suggest an alternative approach by developing acoustically sensitive microcapsule reservoirs that have future applications for treating large ischemic tumors through intratumoral therapy. We call these agents Acoustically Sensitized Microcapsules (ASMs) and these are not planned for the circulation. ASMs are very simple in their formulation, robust and reproducible. They have been designed to offer high payload (because of their large size), be acoustically sensitive and reactive (because of the Ultrasound Contrast Agents (UCAs) encapsulated) and mechanically robust for future injections/implantations within tumors. We describe three different aspects - (1) effect of therapeutic ultrasound; (2) mechanical properties and (3) imaging signatures of these agents. Under therapeutic ultrasound, the formation of a cavitational bubble was seen prior to rupture. The time to rupture was size dependent. Size dependency was also seen when measuring mechanical properties of these ASMs. % Alginate and permeability also affected the Young's modulus estimates. For study of imaging signatures of these agents, we show six schemes. For example, with harmonic imaging, tissue phantoms and controls did not generate higher harmonic components. Only ASM phantoms created a harmonic signal, whose sensitivity increased with applied acoustic pressure. Future work includes developing schemes combining both sonication and imaging to help detect ASMs before, during and after release of drug substance.