Ultrasound-mediated delivery of bioactive nanobubbles to vascular tissue

Abstract

Bubble liposomes (BLs) are under development for ultrasound-triggered release of a potent vasodilator within the vasculature. Nano-sized vesicles facilitate this process by enclosing bubbles to enhance ultrasound image contrast, and deliver therapeutic agents. Assessment of drug delivery in living tissue allows for mechanistic pathways to be revealed. In this study, we used a novel ex vivo model to assess the vascular effects of ultrasound-mediated delivery of a bioactive gas-nitric oxide (NO)-from nanobubble liposomes. Porcine carotid arteries were excised post-mortem and mounted in physiologic buffer. Vascular tone was assessed in real time by coupling the artery to an isometric force transducer. NO-loaded BLs were infused into the lumen of the artery, which was exposed to 1-MHz pulsed ultrasound, while acoustic cavitation emissions were monitored. Changes in vascular tone were concurrently measured and compared to control and sham NO exposures. Our results demonstrate that ultrasound-triggered NO release from BLs induces potent vasorelaxation within porcine carotid arteries. This approach is a valuable mechanistic tool to assess the bioeffects that NO elicits within the vasculature upon release from BLs exposed to 1-MHz ultrasound.