title: Localized in vivo model drug delivery with intravascular ultrasound and microbubbles.
abstract: An intravascular ultrasound (IVUS) and microbubble drug delivery system was evaluated in both ex vivo and in vivo swine vessel models. Microbubbles with the fluorophore DiI embedded in the shell as a model drug were infused into ex vivo swine arteries at a physiologic flow rate (105 mL/min) while a 5-MHz IVUS transducer applied ultrasound. Ultrasound pulse sequences consisted of acoustic radiation force pulses to displace DiI-loaded microbubbles from the vessel lumen to the wall, followed by higher-intensity delivery pulses to release DiI into the vessel wall. Insonation with both the acoustic radiation force pulse and the delivery pulse increased DiI deposition 10-fold compared with deposition with the delivery pulse alone. Localized delivery of DiI was then demonstrated in an in vivo swine model. The theoretical transducer beam width predicted the measured angular extent of delivery to within 11%. These results indicate that low-frequency IVUS catheters are a viable method for achieving localized drug delivery with microbubbles.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Kilroy
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA; Cardiovascular Division, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Klibanov
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA; Cardiovascular Division, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA; Hemoshear, LLC, Charlottesville, Virginia, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Wamhoff
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA.
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Bowles
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA. Electronic address: jh7fj@virginia.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Hossack
mesh_terms: D000818:Animals; D002417:Cattle; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000293:injuries; D016503:Drug Delivery Systems; D054459:Elasticity Imaging Techniques / Q000295:instrumentation*; D045423:Microbubbles; D008856:Microscopy, Fluorescence; D013552:Swine; D014159:Transducers; D018084:Ultrasonography, Interventional / Q000295:instrumentation*
keywords: Acoustic radiation force; Drug delivery; Intravascular ultrasound; In vivo; Microbubbles