Traditional means to identify and treat arterial disease are hampered by an inability to localize atheroma extent and composition. New techniques using targeted echogenic liposomes (ELIP) are being explored as possible solutions to overcome these problems. ELIP are phospholipid vesicles enclosing both aqueous and gaseous spaces. Therapeutics, such as drugs or genes, can be loaded into the ELIP. Furthermore, it has been seen that upon exposure to pulsed ultrasound, the therapeutic can be released from the ELIP and made available for delivery to nearby tissue. The encapsulated gas allows the ELIP to be imaged with a clinical ultrasound scanner and the therapeutic to be delivered via cavitation nucleation. The principal aim of this proposal is to develop techniques that will provide spatially resolved, noninvasive feedback for ultrasound-mediated delivery of a therapeutic to an arterial wall using ELIP. To achieve this aim, two specific aims will be investigated. 1) The acoustic emissions of insonified ELIP, as recorded by a passive ultrasound array, will be correlated with release of an anti-inflammatory (rosiglitazone-cyclodextrin). Subsequently, a spatial map of the emissions, and correlated therapeutic release, will be created. 2) Passive imaging of the insonified ELIP will be correlated with the delivery of the therapeutic to an ex vivo porcine artery. Successful completion of these studies will contribute significantly to the long-term goals of the Holland and McPherson Labs at the Universities of Cincinnati and Texas Health Sciences Center-Houston to trigger and enhance the delivery of a therapeutic for improved physiologic cardiovascular flow.

Public Health Relevance

The proposal seeks to develop passive cavitation images for ultrasound-mediated local release and enhanced delivery of an anti-inflammatory drug for atheroma treatment using echogenic liposomes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL104916-02
Application #
8155319
Study Section
Special Emphasis Panel (ZRG1-F15-D (20))
Program Officer
Meadows, Tawanna
Project Start
2010-09-01
Project End
2012-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2011
Total Cost
$53,512
Indirect Cost
Name
University of Cincinnati
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Klegerman, Melvin E; Naji, Ali K; Haworth, Kevin J et al. (2016) Ultrasound-enhanced bevacizumab release from echogenic liposomes for inhibition of atheroma progression. J Liposome Res 26:47-56
Sutton, J T; Haworth, K J; Shanmukhappa, S K et al. (2016) Delivery of bevacizumab to atheromatous porcine carotid tissue using echogenic liposomes. Drug Deliv 23:3594-3605
Haworth, Kevin J; Raymond, Jason L; Radhakrishnan, Kirthi et al. (2016) Erratum to: ""Trans-stent B-mode Ultrasound and Passive Cavitation Imaging"" in Ultrasound Med Biol 2016;42(2):518-527. Ultrasound Med Biol 42:1244
Haworth, Kevin J; Salgaonkar, Vasant A; Corregan, Nicholas M et al. (2015) Using passive cavitation images to classify high-intensity focused ultrasound lesions. Ultrasound Med Biol 41:2420-34
Haworth, Kevin J; Weidner, Christopher R; Abruzzo, Todd A et al. (2015) Mechanical properties and fibrin characteristics of endovascular coil-clot complexes: relevance to endovascular cerebral aneurysm repair paradigms. J Neurointerv Surg 7:291-6
Raymond, Jason L; Haworth, Kevin J; Bader, Kenneth B et al. (2014) Broadband attenuation measurements of phospholipid-shelled ultrasound contrast agents. Ultrasound Med Biol 40:410-21
Haworth, Kevin; Salgaonkar, Vasant A; Corregan, Nicholas M et al. (2013) Spatial specificity and sensitivity of passive cavitation imaging for monitoring high-intensity focused ultrasound thermal ablation in ex vivo bovine liver. Proc Meet Acoust 19:075022
Sutton, Jonathan T; Haworth, Kevin J; Pyne-Geithman, Gail et al. (2013) Ultrasound-mediated drug delivery for cardiovascular disease. Expert Opin Drug Deliv 10:573-92
Kopechek, Jonathan A; Haworth, Kevin J; Radhakrishnan, Kirthi et al. (2013) The impact of bubbles on measurement of drug release from echogenic liposomes. Ultrason Sonochem 20:1121-30
Radhakrishnan, Kirthi; Bader, Kenneth B; Haworth, Kevin J et al. (2013) Relationship between cavitation and loss of echogenicity from ultrasound contrast agents. Phys Med Biol 58:6541-63

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