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Bubble Inflation Using Phase-Change Perfluorocarbon Nanodroplets as a Strategy for Enhanced Ultrasound Imaging and Therapy. | LitMetric

AI Article Synopsis

  • - Phase-change perfluorocarbon microdroplets were developed over 20 years ago to block blood vessels in medical applications, but their use has been limited due to concerns about effectiveness and safety.
  • - Recent interest has shifted towards perfluorocarbon nanodroplets for better targeting and improving ultrasound treatments, though their clinical testing has not occurred due to unresolved side effects caused by droplets and microbubbles existing together in the bloodstream.
  • - This study reveals that this coexistence leads to significant microbubble expansion from droplet vaporization, which could be controlled through formulation adjustments, suggesting potential for safer application and improved therapeutic outcomes.

Article Abstract

Phase-change perfluorocarbon microdroplets were introduced over 2 decades ago to occlude downstream vessels in vivo. Interest in perfluorocarbon nanodroplets has recently increased to enable extravascular targeting, to rescue the weak ultrasound signal of perfluorocarbon droplets by converting them to microbubbles and to improve ultrasound-based therapy. Despite great scientific interest and advances, applications of phase-change perfluorocarbon agents have not reached clinical testing because of efficacy and safety concerns, some of which remain unexplained. Here, we report that the coexistence of perfluorocarbon droplets and microbubbles in blood, which is inevitable when droplets spontaneously or intentionally vaporize to form microbubbles, is a major contributor to the observed side effects. We develop the theory to explain why the coexistence of droplets and microbubbles results in microbubble inflation induced by perfluorocarbon transfer from droplets to adjacent microbubbles. We also present the experimental data showing up to 6 orders of magnitude microbubble volume expansion, which occludes a 200 μm tubing in the presence of perfluorocarbon nanodroplets. More importantly, we demonstrate that the rate of microbubble inflation and ultimate size can be controlled by manipulating formulation parameters to tailor the agent's design for the potential theranostic application while minimizing the risk to benefit ratio.

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Source
http://dx.doi.org/10.1021/acs.langmuir.9b03647DOI Listing

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