Remote targeted implantation of sound-sensitive biodegradable multi-cavity microparticles with focused ultrasound

Ultrasound-enhanced drug delivery has shown great promise in providing targeted burst release of drug at the site of the disease. Yet current solid ultrasound-responsive particles are non-degradable with limited potential for drug-loading. Here, we report on an ultrasound-responsive multi-cavity poly(lactic-co-glycolic acid) microparticle (mcPLGA MP) loaded with rhodamine B (RhB) with or without 4',6-diamidino-2-phenylindole (DAPI) to represent small molecule therapeutics. After exposure to high intensity focused ultrasound (HIFU), these delivery vehicles were remotely implanted into gel and porcine tissue models, where the particles rapidly released their payload within the first day and sustained release for at least seven days. RhB-mcPLGA MPs were implanted with HIFU into and beyond the sub-endothelial space of porcine arteries without observable damage to the artery. HIFU also guided the location of implantation; RhB-mcPLGA MPs were only observed at the focus of the HIFU away from the direction of ultrasound. Once implanted, DAPI co-loaded RhB-mcPLGA MPs released DAPI into the arterial wall, staining the nucleus of the cells. Our work shows the potential for HIFU-guided implantation of drug-loaded particles as a strategy to improve the local and sustained delivery of a therapeutic for up to two weeks.