Sonothrombolysis with Magnetically Targeted Microbubbles

Abstract

Microbubble-enhanced sonothrombolysis is a promising approach to increasing the tolerability and efficacy of current pharmacological treatments for ischemic stroke. Maintaining therapeutic concentrations of microbubbles and drugs at the clot site, however, poses a challenge. The objective of this study was to investigate the effect of magnetic microbubble targeting upon clot lysis rates in vitro. Retracted whole porcine blood clots were placed in a flow phantom of a partially occluded middle cerebral artery. The clots were treated with a combination of tissue plasminogen activator (0.75 mg/mL), magnetic microbubbles (»10 7 microbubbles/mL) and ultrasound (0.5 MHz, 630-kPa peak rarefactional pressure, 0.2-Hz pulse repetition frequency, 2% duty cycle). Magnetic targeting was achieved using a single permanent magnet (0.08À0.38 T and 12-140 T/m in the region of the clot). The change in clot diameter was measured optically over the course of the experiment. Magnetic targeting produced a threefold average increase in lysis rates, and linear correlation was observed between lysis rate and total energy of acoustic emissions.

Microbubble Agents: New Directions

“…An alternative and potentially complementary targeting approach is to encapsulate magnetic material within the microbubble coating, thereby making the microbubbles responsive to an externally applied magnetic field. Magnetic targeting of microbubbles has been demonstrated to enable enhanced delivery of multiple therapeutics in vitro and in vivo (Stride et al 2009;Vlaskou et al 2010), accelerated thrombolysis (de Saint Victor et al 2019), improved contrast enhancement and to provide magnetic resonance image contrast enhancement (Crake et al 2016).…”

Ultrasound-responsive polymer-based drug delivery systems

“…Advances in ultrasound-guided drug delivery for the treatment of thrombotic diseases have shown potential [171][172][173][174][175]. A novel urokinase-loaded nanogel was designed for ultrasound-triggered thrombolysis [176].…”

Targeted nano-delivery strategies for facilitating thrombolysis treatment in ischemic stroke

“…Magnetic guided targeting is another potential physical strategy which functions by applying an external magnetic field to manipulate magnetic nanoparticles (MNPs) carrying drugs to achieve site-specific targeting, in a controlled method (Ma et al., 2009 ; Yang et al., 2012 ; Chen et al., 2016 ; Tadayon et al., 2016 ; Hu et al., 2018 ; de Saint Victor et al., 2019 ; Liu et al., 2019 ; Zhang et al., 2019 ). MNPs are suitable candidates for a multitude of biomedical applications not limited to drug delivery including imaging and biosensing, and the combination of these functions makes it possible to realize the diagnosis and treatment of diseases simultaneously, making it a popular clinical pattern of theranostics.…”