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
Haworth, Kevin J; Bader, Kenneth B; Rich, Kyle T et al. (2017) Quantitative Frequency-Domain Passive Cavitation Imaging. IEEE Trans Ultrason Ferroelectr Freq Control 64:177-191
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
Raymond, Jason L; Luan, Ying; Peng, Tao et al. (2016) Loss of gas from echogenic liposomes exposed to pulsed ultrasound. Phys Med Biol 61:8321-8339
Haworth, Kevin J; Raymond, Jason L; Radhakrishnan, Kirthi et al. (2016) Trans-Stent B-Mode Ultrasound and Passive Cavitation Imaging. Ultrasound Med Biol 42:518-27
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
Raymond, Jason L; Luan, Ying; van Rooij, Tom et al. (2015) Impulse response method for characterization of echogenic liposomes. J Acoust Soc Am 137:1693-703
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
Radhakrishnan, Kirthi; Haworth, Kevin J; Peng, Tao et al. (2015) Loss of echogenicity and onset of cavitation from echogenic liposomes: pulse repetition frequency independence. Ultrasound Med Biol 41:208-21

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