Ultrasound radiation force enables targeted deposition of model drug carriers loaded on microbubbles

Abstract

A novel drug delivery vehicle that specifically targets using ultrasound radiation force (USRF) and biotin–avidin interactions is presented. Model vehicles consist of avidinated fluorescent nanobeads bound directly to the biotinylated lipid shells of preformed microbubbles. USRF was used to deflect the vehicle from the center of flow to a tube surface in order to facilitate receptor–ligand mediated adhesion. At wall shear stress levels commensurate with venous and arterial flow, USRF was used to direct the vehicles to a biotinylated tube surface. Subsequent high-pressure pulses fragmented the carrier, and molecular interactions induced deposition of the nanobeads on the wall. Targeting of nanobeads to the tube was molecularly specific and dependent on, in order of importance, vehicle concentration, wall shear stress, nanobead size, and insonation time. The observation that portions of the microbubble lipid monolayer shell remain attached to adherent nanobeads is important for future consideration of drug transport mechanisms. This versatile method of delivery is shown to enable targeted deposition of nanoparticles in shear flow and could be modified to carry therapeutic agents for controlled release in targeted delivery applications.