Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics

Ultrasound in Medicine & Biology
Andrew HealeyJonny Østensen

Abstract

Acoustic cluster technology (ACT) is a two-component, microparticle formulation platform being developed for ultrasound-mediated drug delivery. Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a positively charged surface membrane to form microbubble/microdroplet clusters. On exposure to ultrasound, the oil undergoes a phase change to the gaseous state, generating 20- to 40-μm ACT bubbles. An acoustic transmission technique is used to measure absorption and velocity dispersion of the ACT bubbles. An inversion technique computes bubble size population with temporal resolution of seconds. Bubble populations are measured both in vitro and in vivo after activation within the cardiac chambers of a dog model, with catheter-based flow through an extracorporeal measurement flow chamber. Volume-weighted mean diameter in arterial blood after activation in the left ventricle was 22 μm, with no bubbles >44 μm in diameter. After intravenous administration, 24.4% of the oil is activated in the cardiac chambers.

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Citations

Jun 15, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Annemieke van WamelCatharina de Lange Davies
Jul 31, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kinam Park
Jun 27, 2020·Advanced Drug Delivery Reviews·Tao SunSamir Mitragotri
Jul 19, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Marieke OlsmanCatharina de Lange Davies
Aug 31, 2021·ACS Biomaterials Science & Engineering·Kahkashan BansalHimanshu Shekhar

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