Journal
JOURNAL OF CONTROLLED RELEASE
Volume 144, Issue 3, Pages 288-295Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2010.02.030
Keywords
Ultrasound-assisted delivery; Liposomes; ICAM-1 targeting; Vascular endothelium; Atheroma
Funding
- NINDS, NIH [NS047603]
- NIGMS, NIH [T32GM063483]
- Albert J. Ryan Foundation
- Rindsberg Memorial Fund
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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. (C) 2010 Elsevier B.V. All rights reserved.
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