Reducing Neointima Formation in a Swine Model with IVUS and Sirolimus Microbubbles

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Drug Delivery Systems

Background:

• Potent drugs with dose-dependent side effects necessitate improved drug delivery methods.
• Reducing systemic drug doses is crucial for minimizing adverse effects.
• Current drug delivery often lacks sufficient selectivity and efficiency.

Purpose of the Study:

• To develop and evaluate a novel platform combining intravascular ultrasound (IVUS) and drug-loaded microbubbles.
• To enhance and localize drug delivery for therapeutic applications.
• To assess the versatility of this platform for different drug types and dosing strategies.

Main Methods:

• Ex vivo assessment of IVUS and microbubble-mediated delivery using fluorophore-loaded microbubbles in swine arteries.
• In vivo evaluation in a swine model of neointimal hyperplasia using IVUS and sirolimus-loaded microbubbles.
• Optimization of IVUS parameters (e.g., low amplitude pulses) for enhanced delivery.

Main Results:

• IVUS and microbubble-enhanced fluorophore delivery was maximized with low amplitude pulses in ex vivo models.
• Neointima formation was reduced by 50% in vivo following treatment with IVUS and sirolimus-loaded microbubbles.
• Achieved therapeutic sirolimus blood concentration was comparable to commercial drug-eluting stents.

Conclusions:

• The combined IVUS and microbubble platform offers an effective strategy for localized drug delivery.
• This technology shows significant potential for treating atherosclerosis as an adjunct to stenting.
• The platform's versatility suggests broad clinical applications for various diseases requiring targeted drug delivery.