In vitro studies of a new thrombus-specific ultrasound contrast agent

Unger, Evan C.; McCreery, Thomas P.; Sweitzer, Robert H.; Shen, De Kang; Wu, Guanhui

doi:10.1016/s0002-9149(98)00055-1

Cited by 155 publications

(92 citation statements)

References 15 publications

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“…The liposomes are composed of phospholipid bilayers encapsulating a liquid core and gas pocket. The exact location and size of the gas pockets within the liposome is unknown, but these pockets most likely exist on the hydrophobic side of the lipid or within a lipid monolayer in the aqueous compartment (Unger et al, 1998). Lipid monolayers surround and stabilize the gas within the fluid-filled liposomes .…”

Section: Introductionmentioning

confidence: 99%

Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound

Gruber

Bader

Holland

2014

The Journal of the Acoustical Society of America

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Ultrasound contrast agents (UCAs) can be employed to nucleate cavitation to achieve desired bioeffects, such as thrombolysis, in therapeutic ultrasound applications. Effective methods of enhancing thrombolysis with ultrasound have been examined at low frequencies (<1 MHz) and low amplitudes (<0.5 MPa). The objective of this study was to determine cavitation thresholds for two UCAs exposed to 120-kHz ultrasound. A commercial ultrasound contrast agent (Definity V R ) and echogenic liposomes were investigated to determine the acoustic pressure threshold for ultraharmonic (UH) and broadband (BB) generation using an in vitro flow model perfused with human plasma. Cavitation emissions were detected using two passive receivers over a narrow frequency bandwidth (540-900 kHz) and a broad frequency bandwidth (0.54-1.74 MHz). UH and BB cavitation thresholds occurred at the same acoustic pressure (0.3 6 0.1 MPa, peak to peak) and were found to depend on the sensitivity of the cavitation detector but not on the nucleating contrast agent or ultrasound duty cycle.

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Section: Introductionmentioning

confidence: 99%

Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound

Gruber

Bader

Holland

2014

The Journal of the Acoustical Society of America

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“…Upon examination with an ultrasound medical imaging system, the adherent microbubbles generate an acoustic response signal that is displayed as video enhancement of the target tissue on the system screen. Targeted ultrasound contrast agents have been used to assess vascular pathology associated with several intravascular markers, including P-selectin [3], ICAM-1 [4,5], GpIIb/IIIa [6,7], the α v integrins [8,9] and other markers of tumor angiogenesis [10]. Successful targeted contrast ultrasound imaging in these systems is possible in part due to extremely high microbubble detection sensitivity of ultrasound imaging, with the capability to visualize individual microbubbles [11].…”

Section: Introductionmentioning

confidence: 99%

Deformable gas-filled microbubbles targeted to P-selectin

Rychak

Lindner

Ley

et al. 2006

Journal of Controlled Release

116

104

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Ultrasound contrast microbubbles have been successfully targeted to a number of intravascular disease markers. We hypothesized that targeted delivery could be improved further, by making the microbubbles deformable, leading to increased microbubble-endothelium adhesion contact area and stabilized adhesion. Activated leukocytes utilize such strategy; they deform after binding to inflamed endothelium in the vasculature. Lipid-shell microbubbles were targeted to the endothelial inflammatory protein P-selectin with a monoclonal anti-P-selectin antibody attached to the microbubble shell. Deformable microbubbles were created by controlled pressurization with partial gas loss, which generated an average excess shell surface area of ∼30% and the formation of outward-projected wrinkles and folds. Targeted microbubble adhesion and deformability were assessed in the parallel plate flow chamber under shear flow. Sustained adhesion of deformable microbubbles at wall shear stresses between 0.4 and 1.35 dyn/cm 2 was consistently better than adhesion of wrinkle-free microbubbles. Over this shear range, targeted wrinkled microbubbles were deformed by shear flow, unlike wrinkle-free microbubbles. In a murine cremaster inflammation model, a significant improvement of deformable microbubble targeting was observed by intravital microscopy. Overall, the mechanical aspects of adhesion, such as particle shape, deformability and surface microstructure, are important in engineering efficient site-targeted particle-based agents for medical imaging and therapy.

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“…Platelets, which exist in high concentrations on the surface of thrombi, can be targeted by conjugating a glycoprotein (GP) IIb/IIIa receptor inhibitor to the delivery vesicle [200][201][202][203][204]. Investigations implementing this targeting strategy show enhanced thrombolysis in the presence of a thrombolytic and targeted microbubbles exposed to US.…”

Section: Drug Targetingmentioning

confidence: 99%

Ultrasound-Mediated Drug Delivery for Cardiovascular Disease

Holland

2017

Ultrasound in Medicine & Biology

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Introduction-Ultrasound (US) has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. These effects can be mediated by mechanical oscillations of circulating microbubbles, or US contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi or direct drugs to optimal locations for delivery.Areas covered-The present review summarizes investigations that have provided evidence for US-mediated drug delivery as a potent method to deliver therapeutics to diseased tissue for cardiovascular treatment. In particular, the focus will be on investigations of specific aspects relating to US-mediated drug delivery, such as delivery vehicles, drug transport routes, biochemical mechanisms and molecular targeting strategies.Expert opinion-These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery and new US technologies. Successful implementation of US-mediated drug delivery has the potential to change the way many drugs are administered systemically, resulting in more effective and economical therapeutics, and lessinvasive treatments.

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In vitro studies of a new thrombus-specific ultrasound contrast agent

Cited by 155 publications

References 15 publications

Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound

Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound

Deformable gas-filled microbubbles targeted to P-selectin

Ultrasound-Mediated Drug Delivery for Cardiovascular Disease

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