title: Reducing Neointima Formation in a Swine Model with IVUS and Sirolimus Microbubbles.
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.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Kilroy
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Dhanaliwala
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA.|School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Klibanov
authors.affiliation: Department of Veterinary Sciences, University of Missouri, Columbia, MO, USA.
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Bowles
authors.affiliation: HemoShear, LLC, Charlottesville, VA, 22903, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Wamhoff
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA. jh7fj@virginia.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Hossack
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D003331:Coronary Vessels / Q000473:pathology; D016503:Drug Delivery Systems; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D045423:Microbubbles; D058426:Neointima / Q000188:drug therapy* / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D013552:Swine; D018084:Ultrasonography, Interventional
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus
keywords: Angioplasty; Atherosclerosis; Neointimal hyperplasia; Ultrasound