Sonothrombolysis efficacy of microbubbles produced by a microfluidic device in a rat ischemic stroke model

Sonothrombolysis traditionally uses microbubble (MB) formulations comprised of low solubility gases with diameters between 1–4 µm. MBs with parameters outside of this range have not been explored for sonothrombolysis due to embolic risks associated with large diameter, insoluble MBs. However, a growing body of evidence suggests that larger MBs confer increased bioeffects when excited acoustically, as has been demonstrated in BBB disruption, sonoporation, and sonothrombolysis studies. In this work, we demonstrate that sonothrombolysis using MBs of 10–20 µm diameter reduces cerebral infarct volumes in a rat stroke model by up to approximately 50% (versus no therapy) and permit a tPA dose reduction of 3–7 fold when compared to tPA-only therapy. This in vivo study builds on our previous in vitro results that demonstrated an approximate 4.5-fold increase in sonothrombolysis rates when using MBs with 10–20 µm diameter versus small MBs of 2 µm diameter.