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

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Abstract

Potent therapeutic compounds with dose dependent side effects require more efficient and selective drug delivery to reduce systemic drug doses. Here, we demonstrate a new platform that combines intravascular ultrasound (IVUS) and drug-loaded microbubbles to enhance and localize drug delivery, while enabling versatility of drug type and dosing. Localization and degree of delivery with IVUS and microbubbles was assessed using fluorophore-loaded microbubbles and different IVUS parameters in ex vivo swine arteries. Using a swine model of neointimal hyperplasia, reduction of neointima formation following balloon injury was evaluated when using the combination of IVUS and sirolimus-loaded microbubbles. IVUS and microbubble enhanced fluorophore delivery was greatest when applying low amplitude pulses in the ex vivo model. In the in vivo model, neointima formation was reduced by 50% after treatment with IVUS and the sirolimus-loaded microbubbles. This reduction was achieved with a sirolimus whole blood concentration comparable to a commercial drug-eluting stent (0.999 ng/mL). We anticipate this therapy will find clinical use localizing drug delivery for numerous other diseases in addition to serving as an adjunct to stents in treating atherosclerosis.

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Acknowledgments

The authors would like to acknowledge Gore Processing Inc. of Edinburg, VA for providing tissue samples and Jan Ivey and Darla Tharp, PhD for their assistance and technical expertise during the in vivo swine experiments. This work was supported by NIH National Heart Lung and Blood Institute award HL090700, National Institute of General Medical Sciences award T32GM008715, and the University of Virginia Coulter Translational Research Grant. The opinions expressed in this article are those of the authors and do not reflect any official position of the NIH.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA

    Joseph P. Kilroy, Ali H. Dhanaliwala, Alexander L. Klibanov & John A. Hossack

  2. School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA

    Alexander L. Klibanov

  3. Department of Veterinary Sciences, University of Missouri, Columbia, MO, USA

    Douglas K. Bowles

  4. HemoShear, LLC, Charlottesville, VA, 22903, USA

    Brian R. Wamhoff

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  1. Joseph P. Kilroy
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Correspondence to John A. Hossack.

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Kilroy, J.P., Dhanaliwala, A.H., Klibanov, A.L. et al. Reducing Neointima Formation in a Swine Model with IVUS and Sirolimus Microbubbles. Ann Biomed Eng 43, 2642–2651 (2015). https://doi.org/10.1007/s10439-015-1315-6

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