title: Ultrasound-enhanced delivery of targeted echogenic liposomes in a novel ex vivo mouse aorta model.
abstract: The goal of this study was to determine whether targeted, Rhodamine-labeled echogenic liposomes (Rh-ELIP) containing nanobubbles could be delivered to the arterial wall, and whether 1-MHz continuous wave ultrasound would enhance this delivery profile. Aortae excised from apolipoprotein-E-deficient (n=8) and wild-type (n=8) mice were mounted in a pulsatile flow system through which Rh-ELIP were delivered in a stream of bovine serum albumin. Half the aortae from each group were treated with 1-MHz continuous wave ultrasound at 0.49 MPa peak-to-peak pressure, and half underwent sham exposure. Ultrasound parameters were chosen to promote stable cavitation and avoid inertial cavitation. A broadband hydrophone was used to monitor cavitation activity. After treatment, aortic sections were prepared for histology and analyzed by an individual blinded to treatment conditions. Delivery of Rh-ELIP to the vascular endothelium was observed, and sub-endothelial penetration of Rh-ELIP was present in five of five ultrasound-treated aortae and was absent in those not exposed to ultrasound. However, the degree of penetration in the ultrasound-exposed aortae was variable. There was no evidence of ultrasound-mediated tissue damage in any specimen. Ultrasound-enhanced delivery within the arterial wall was demonstrated in this novel model, which allows quantitative evaluation of therapeutic delivery.
authors.affiliation: Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, United States. hitchcke@email.uc.edu
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Hitchcock
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Caudell
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Sutton
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Klegerman
authors.forename: Deborah
authors.initials: D
authors.lastname: Vela
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Pyne-Geithman
authors.forename: Todd
authors.initials: T
authors.lastname: Abruzzo
authors.forename: Peppar E P
authors.initials: PE
authors.lastname: Cyr
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Geng
authors.forename: David D
authors.initials: DD
authors.lastname: McPherson
authors.forename: Christy K
authors.initials: CK
authors.lastname: Holland
mesh_terms: D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D004867:Equipment Design; D005260:Female; D066298:In Vitro Techniques; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D023421:Models, Animal; D012235:Rhodamines / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D014465:Ultrasonics; D014463:Ultrasonography
chemical_list: D001057:Apolipoproteins E; D008051:Lipid Bilayers; D008081:Liposomes; D012235:Rhodamines