Characterization and Imaging of Lipid-Shelled Microbubbles for Ultrasound-Triggered Release of Xenon

Shekhar, Himanshu; Palaniappan, Arunkumar; Peng, Tao; Lafond, Maxime; Moody, Melanie R.; Haworth, Kevin J.; Huang, Shaoling; McPherson, David D.; Holland, Christy K.

doi:10.1007/s13311-019-00733-4

Cited by 26 publications

(14 citation statements)

References 65 publications

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“…An ultrasound microbubble contrast agent is a liquid solution containing bubbles with a diameter between 1 and 8 μ m, which are injected into human blood vessels to enhance the ultrasound signal of blood flow, thereby improving the clarity and resolution of resulting ultrasound images [ 9 , 10 ]. Due to the limited flexibility of human blood cells and the ability of microbubbles to increase the spacing between human tissues, the microbubbles can enhance ultrasound signals.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of Atherosclerotic Plaques Using Vascular Endothelial Growth Factor Receptor-2 Targeting Antibody Nano-microbubble as Ultrasound Contrast Agent

Wang

Feng

Yang

et al. 2022

Computational and Mathematical Methods in Medicine

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The atherosclerotic plaque is characterized by narrowing of blood vessels and reduced blood flow leading to the insufficient blood supply to the brain. The hemodynamic changes caused by arterial stenosis increase the shearing force of the fibrous cap on the surface of the plaque, thereby reducing the stability of the plaque. Unstable plaques are more likely to promote angiogenesis and increase the risk of patients with cerebrovascular diseases. A timely understanding of the formation and stability of the arterial plaque can guide in taking targeted measures for reducing the risk of acute stroke in patients. It has been confirmed that nano-microbubbles can enter these plaques through the gaps in the patient’s vascular endothelial cells, thereby enhancing the acquisition of ultrasound information for plaque visualization. Therefore, we aim to investigate the diagnostic value of targeted nano-microbubbles for atherosclerotic plaques. This study constructed vascular endothelial growth factor receptor-2 (VEGFR-2) targeting antibody nano-microbubbles and compared its diagnostic value with that of blank nano-microbubbles for atherosclerotic plaques. Studies have found that VEGFR-2 targeting antibody nano-microbubbles can accurately detect the position of plaques. Its detection rate, sensitivity, and specificity for plaques are higher than those of blank nano-microbubbles. Similarly, the peak intensity and average transit time of VEGFR-2 targeting antibody nano-microbubbles were greater than those of blank nano-microbubbles. Therefore, we believe that the combination of VEGFR-2 antibody and nano-microbubbles can enhance the acquisition of ultrasound information on atherosclerotic plaque neovascularization, thereby improving the early diagnosis of unstable plaque.

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Section: Introductionmentioning

confidence: 99%

Diagnosis of Atherosclerotic Plaques Using Vascular Endothelial Growth Factor Receptor-2 Targeting Antibody Nano-microbubble as Ultrasound Contrast Agent

Wang

Feng

Yang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…112 Interestingly, Shekhar et al demonstrated effective encapsulation and ultrasound-triggered (6 MHz Doppler, MI 0.8 and 220 kHz pulsed, MI 0.47, 10 seconds) delivery of xenon to the brain in a mouse model using a DSPC/DSPE-PEG2000 (9 : 1 ratio) lipid-shelled microbubble loaded with xenon and octafluoropropane, to help reduce and stabilize neurologic injury in stroke. 113 Most excitingly, since 2018, several small (4-5 patients per study) phase I safety and feasibility studies on permeabilizing the BBB in humans using focused ultrasound techniques have been reported with no serious clinical or radiological side effects. [114][115][116] A representative image from one of these studies, demonstrating visible BBB opening, is shown in Fig.…”

Section: Reviewmentioning

confidence: 99%

Making waves: how ultrasound-targeted drug delivery is changing pharmaceutical approaches

et al. 2022

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“…To prepare NO-loaded MB, 1,2distearoyl-sn-glycero-3-phosphocholine (DSPC), and 1,2distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (18:0 PEG2000 PE) were combined in a molar ratio of 9:1. The procedure for preparing these lipidshelled MB has been reported in detail previously (Shekhar et al, 2019b). Briefly, a thin lipid film was formed in a round bottom flask using a rotary evaporator (N-1001, Eyela, Bohemia, NY).…”

Section: Preparation Of Lipid-shelled Mbmentioning

confidence: 99%

“…Recent studies on bioactive gas delivery suggest that the bioactive gas payload can be stabilized by the co-encapsulation of perfluorocarbon gases (Kwan et al, 2012;Yang et al, 2018;Shekhar et al, 2019b). Whether co-encapsulation of a perfluorocarbon gas can stabilize NO payload within MB has not been determined previously.…”

Section: Introductionmentioning

confidence: 99%

Bactericidal Activity of Lipid-Shelled Nitric Oxide-Loaded Microbubbles

Lafond¹,

Shekhar²,

Panmanee³

et al. 2020

Front. Pharmacol.

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The global pandemic of antibiotic resistance is an ever-burgeoning public health challenge, motivating the development of adjunct bactericidal therapies. Nitric oxide (NO) is a potent bioactive gas that induces a variety of therapeutic effects, including bactericidal and biofilm dispersion properties. The short half-life, high reactivity, and rapid diffusivity of NO make therapeutic delivery challenging. The goal of this work was to characterize NO-loaded microbubbles (MB) stabilized with a lipid shell and to assess the feasibility of antibacterial therapy in vitro. MB were loaded with either NO alone (NO-MB) or with NO and octafluoropropane (NO-OFP-MB) (9:1 v/v and 1:1 v/v). The size distribution and acoustic attenuation coefficient of NO-MB and NO-OFP-MB were measured. Ultrasound-triggered release of the encapsulated gas payload was demonstrated with 3-MHz pulsed Doppler ultrasound. An amperometric microelectrode sensor was used to measure NO concentration released from the MB and compared to an NO-OFP-saturated solution. The effect of NO delivery on the viability of planktonic (free living) Staphylococcus aureus (SA) USA 300, a methicillin-resistant strain, was evaluated in a 96 well-plate format. The co-encapsulation of NO with OFP increased the total volume and attenuation coefficient of MB. The NO-OFP-MB were destroyed with a clinical ultrasound scanner with an output of 2.48 MPa peak negative pressure (in situ MI of 1.34) but maintained their echogenicity when exposed to 0.02 MPa peak negative pressure (in situ MI of 0.01. The NO dose in NO-MB and NO-OFP-MB was more than 2-fold higher than the NO-OFPsaturated solution. Delivery of NO-OFP-MB increased bactericidal efficacy compared to the NO-OFP-saturated solution or air and OFP-loaded MB. These results suggest that encapsulation of NO with OFP in lipid-shelled MB enhances payload delivery. Furthermore, these studies demonstrate the feasibility and limitations of NO-OFP-MB for antibacterial applications.

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Characterization and Imaging of Lipid-Shelled Microbubbles for Ultrasound-Triggered Release of Xenon

Cited by 26 publications

References 65 publications

Diagnosis of Atherosclerotic Plaques Using Vascular Endothelial Growth Factor Receptor-2 Targeting Antibody Nano-microbubble as Ultrasound Contrast Agent

Diagnosis of Atherosclerotic Plaques Using Vascular Endothelial Growth Factor Receptor-2 Targeting Antibody Nano-microbubble as Ultrasound Contrast Agent

Making waves: how ultrasound-targeted drug delivery is changing pharmaceutical approaches

Bactericidal Activity of Lipid-Shelled Nitric Oxide-Loaded Microbubbles

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