Focused Ultrasound-Mediated Drug Delivery From Microbubbles Reduces Drug Dose Necessary for Therapeutic Effect on Neointima Formation—Brief Report

Abstract

OBJECTIVE: We hypothesized that (1) neointima formation in a rat carotid balloon injury model could be reduced in vivo following targeted ultrasound delivery of rapamycin microbubbles (RMBs), and (2) the addition of dual-mode ultrasound decreases the total amount of drug needed to reduce neointima formation. METHODS AND RESULTS: Balloon injury was performed in rat carotids to induce neointima formation. High or low doses of RMBs were injected intravenously and ruptured at the site of injury with ultrasound. Compared with nontreated injured arteries, neointima formation was reduced by 0% and 35.9% with 10(8) RMBs and by 28.7% and 34.9% in arteries treated with 10(9) RMBs with and without ultrasound, respectively. CONCLUSIONS: Without ultrasound, 10-fold higher concentrations of RMBs were needed to reduce neointima formation by at least 28%, whereas 10(8) RMBs combined with ultrasound were sufficient to achieve the same therapeutic effect, demonstrating that this technology may have promise for localized potent drug therapy.