Traditional means to identify and treat arterial disease are hampered by their inability to localize atheroma components. Novel targeted acoustic, highlighting, and delivery agents, such as liposomes, may overcome these problems. Liposomes are phospholipid vesicles enclosing an aqueous space. We have developed a unique methodology that, by process and composition, makes these liposomes echogenic. This formulation allows modification for antibody conjugation and therapeutic drug/gene incorporation. Work by this group has demonstrated that these formulations can incorporate therapeutics and deliver drugs and genes to cells, while retaining their echogenic properties. The addition of therapeutic ultrasound has an added unique effect on these echogenic liposomes by increasing cellular delivery. Our principal aim is to develop a model carrier and a technique that has the ability to incorporate a therapeutic with delivery to a target structure while retaining the therapeutic's effects. To this end, we will;a) develop optimal therapeutic echogenic immunoliposomes;b) develop optimal ultrasound parameters for therapeutic delivery of loaded ELIP and c) determine the efficacy of our therapeutic ELIP in slowing/stabilizing atheroma progression. We will use 3 novel therapeutics (rosiglitazone)anti- inflammatory;(bevacizumab) anti-angiogenesis;and (eNOS) anti-inflammatory gene. Our long term goals would be to deliver the therapeutic loaded ELIP simultaneously with ultrasound exposure, in patients, to trigger drug or gene delivery and enhance uptake in targeted vascular beds. By focusing our experiments in this direction, we would then be able to transition our techniques into the clinical setting to allow investigators to apply more directed therapy to improve physiologic cardiovascular flow.

Public Health Relevance

This proposal seeks to develop a stable formulation (echogenic immunoliposomes) that has the ability to incorporate a therapeutic with delivery to a target structure while retaining the therapeutic's effect.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL074002-07
Application #
8239546
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Buxton, Denis B
Project Start
2003-07-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
7
Fiscal Year
2012
Total Cost
$726,158
Indirect Cost
$179,372
Name
University of Texas Health Science Center Houston
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Sutton, J T; Raymond, J L; Verleye, M C et al. (2014) Pulsed ultrasound enhances the delivery of nitric oxide from bubble liposomes to ex vivo porcine carotid tissue. Int J Nanomedicine 9:4671-83
Klegerman, Melvin E; Zou, Yuejiao; Golunski, Eva et al. (2014) Use of thermodynamic coupling between antibody-antigen binding and phospholipid acyl chain phase transition energetics to predict immunoliposome targeting affinity. J Liposome Res 24:216-22
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
Kim, Hyunggun; Britton, George L; Peng, Tao et al. (2014) Nitric oxide-loaded echogenic liposomes for treatment of vasospasm following subarachnoid hemorrhage. Int J Nanomedicine 9:155-65
Kee, Patrick H; Kim, Hyunggun; Huang, Shaoling et al. (2014) Nitric oxide pretreatment enhances atheroma component highlighting in vivo with intercellular adhesion molecule-1-targeted echogenic liposomes. Ultrasound Med Biol 40:1167-76
Bader, Kenneth B; Holland, Christy K (2013) Gauging the likelihood of stable cavitation from ultrasound contrast agents. Phys Med Biol 58:127-44
Rim, Yonghoon; McPherson, David D; Kim, Hyunggun (2013) Volumetric three-dimensional intravascular ultrasound visualization using shape-based nonlinear interpolation. Biomed Eng Online 12:39
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
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
Kim, Hyunggun; Kee, Patrick H; Rim, Yonghoon et al. (2013) Nitric oxide improves molecular imaging of inflammatory atheroma using targeted echogenic immunoliposomes. Atherosclerosis 231:252-60

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