Delivery of drug, or gene, to blood vessel wall using intravascular ultrasound and microbubbles.

Abstract

Atherosclerotic arteries are routinely treated using balloon angioplasty followed by stent placement. We developed a concept for a new therapy to prevent restenosis involving using ultrasound and microbubble‐based drug/gene carriers. A number of early in vitro and in vivo results are presented. In particular, data for delivery of antiproliferative gene via microbubbles ruptured via catheter‐based intravascular ultrasound (IVUS) at the site of vessel injury in vivo in a pig coronary artery are presented. Optimal design of a modified IVUS catheter is discussed. The proposed catheter includes a bubble port, an elongated single element transducer to provide radiation force to cause the bubbles to traverse to the vessel wall, and a bubble rupture transducer. The bubble rupture transducer is ideally coincident with an imaging IVUS scanning single element or annular phased array. These requirements provide the impetus to develop enhanced designs of both PZT based transducers and silicon micromachined transducers. In our initial pig study, transfection efficiency was measured using fluorescence microscopy and quantified as the percent of vessel perimeter cells expressing red fluorescent protein. We observed 23.3±6.0% transfection in the treated vessel whereas the control exhibited 3.6±2% transfection.