Traditional means to identify the physiological severity of arterial disease are hampered by their inability to identify atheroma extent and composition. New techniques that identify atheroma in vivo are being developed, however, accurate methodologies for atheroma characterization are hampered, due to the heterogeneous nature of the disease process. Novel acoustic targeting and highlighting 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, provides acoustic characteristics of liposomes. This formulation allows modification for antibody conjugation and therapeutic drug incorporation. Preliminary work by this group has been centered on the optimization of formulation, optimization of conjugation, and development of in vitro and in vivo quantitation techniques. This proposal describes a series of protocols to optimize highlighting and enhancing characteristics of these formulations in vitro and in vivo. Robust quantitative methodologies will be utilized. We plan to determine in vitro and in vivo transfection and drug delivery potential of these formulations. We plan to investigate the potential of these formulations to aid other imaging modalities as atheroma enhancement agents. Our long term goals are to determine, quantitate, and characterize the stage, extent, and physiologic severity of atherosclerosis and allow directed therapy to improve physiologic flow following intervention.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56HL059586-08
Application #
7625421
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Buxton, Denis B
Project Start
1998-06-01
Project End
2010-05-31
Budget Start
2008-06-15
Budget End
2010-05-31
Support Year
8
Fiscal Year
2008
Total Cost
$480,216
Indirect Cost
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
Miao, Yi-Feng; Peng, Tao; Moody, Melanie R et al. (2018) Delivery of xenon-containing echogenic liposomes inhibits early brain injury following subarachnoid hemorrhage. Sci Rep 8:450
Klegerman, Melvin E; Moody, Melanie R; Hurling, Jermaine R et al. (2017) Gas chromatography/mass spectrometry measurement of xenon in gas-loaded liposomes for neuroprotective applications. Rapid Commun Mass Spectrom 31:1-8
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
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
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
Gruber, Matthew J; Bader, Kenneth B; Holland, Christy K (2014) Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound. J Acoust Soc Am 135:646-53
Rim, Yonghoon; McPherson, David D; Kim, Hyunggun (2013) Volumetric three-dimensional intravascular ultrasound visualization using shape-based nonlinear interpolation. Biomed Eng Online 12:39
Peng, Tao; Britton, George L; Kim, Hyunggun et al. (2013) Therapeutic time window and dose dependence of xenon delivered via echogenic liposomes for neuroprotection in stroke. CNS Neurosci Ther 19:773-84
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

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