Effects of combining low frequency ultrasound irradiation with papaverine on the permeability of the blood–tumor barrier

Wang, Jing-e; Liu, Yunhui; Li, Libo; Chun-yi, Xia; Zhang, Zhen; Xue, Yixue

doi:10.1007/s11060-010-0321-7

Cited by 13 publications

(16 citation statements)

References 56 publications

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“…Other factors such as the delay between the microbubble injection and the start of sonication, and whether the drug or tracer is administered before or after the sonication may also be expected to have an effect. Additive effects have been observed when FUS-induced BBB disruption is combined with agents that affect vascular permeability [100–102]. …”

Section: Ultrasound-induced Bbb Disruptionmentioning

confidence: 99%

Ultrasound-mediated blood–brain barrier disruption for targeted drug delivery in the central nervous system

Aryal

Arvanitis

Alexander

et al. 2014

Advanced Drug Delivery Reviews

362

237

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The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB.

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Section: Ultrasound-induced Bbb Disruptionmentioning

confidence: 99%

Ultrasound-mediated blood–brain barrier disruption for targeted drug delivery in the central nervous system

Aryal

Arvanitis

Alexander

et al. 2014

Advanced Drug Delivery Reviews

362

237

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“…VEGF‐A 165 is the main effective molecule, which can increase vascular permeability, and as a result the surrounding tissues (such as plasma fibrinogen) are extravasated (Senger et al, ; Bairey et al, ). Meanwhile, as we previously reported, VEGF increased permeability of the BTB through the transcellular pathway, and the molecular mechanism might be associated with upregulated expression of caveolin‐1 and caveolin‐2 (Wang et al, ). However, it is still unclear whether VEGF opens the BTB by the paracellular pathway.…”

mentioning

confidence: 58%

“…We previously reported that permeability of the BTB was increased after PA injection and that interleukin‐1β might be involved in this process. Meanwhile, we have demonstrated that significantly downregulated expression of ZO‐1, occludin, and claudin‐5 might be one of the molecular mechanisms of combining low‐frequency ultrasound and PA, enhancing permeability of the BTB (Wang et al, ). However, whether PA increases permeability of the BTB by the transcellular pathway is unclear.…”

mentioning

confidence: 99%

Permeability of the blood–tumor barrier is enhanced by combining vascular endothelial growth factor with papaverine

Yang

Zhao

et al. 2014

J of Neuroscience Research

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This study aims to determine the effects of vascular endothelial growth factor (VEGF), papaverine (PA), and the combination of VEGF and PA on the permeability of the blood-tumor barrier (BTB) and to determine possible molecular mechanisms contributing to the effects. In the rat C6 glioma model, the extravasation of Evans blue (EB) through the BTB was increased significantly by VEGF and PA. VEGF-induced and PA-induced increase of EB extravasation was further increased after combining VEGF with PA infusion. Transmission electron microscopy (TEM) showed that the combination of VEGF and PA not only opened tight junctions (TJ) dramatically but increased the presence of pinocytotic vesicles of brain microvascular endothelial cells (BMECs) significantly. Meanwhile, the downregulation of the TJ-associated proteins occludin and claudin-5 and the upregulation of the caveolae structure proteins caveolin-1 and caveolin-2 caused by the combination of VEGF and PA were observed by Western blot and immunohistochemistry, which were more remarkable than those by the two strategies separately. In addition, after VEGF and PA infusion, the results of radioimmunoassay, Western blot, and enzyme-linked immunosorbent assay (ELISA) revealed a significant increase in expression levels of cGMP and protein kinase G-1 (PKG-1) and the activation of nuclear factor-κB (NF-κB) p65. This study demonstrates that combination of VEGF and PA can increase the permeability of the BTB by a paracellular pathway (downregulation of occludin and claudin-5) and a transcellular pathway (upregulation of caveolin-1 and caveolin-2) and that the cGMP/PKG/NF-κB signal pathway might be involved in the modulation process.

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“…Electron microscopy studies have demonstrated an increase in both transcellular transport [44-50] and paracellular passage [45-48, 50-52] following disruption of the BBB and Blood-Tumor Barrier (BTB) with ultrasound and microbubbles.…”

Section: Mechanismsmentioning

confidence: 99%

“…The time for the BBB to be restored following disruption has been investigated in several studies. The majority of studies report that the BBB generally closes within 24 hours when tissue damage is avoided, and most often within 6-12 hours [24, 46, 48, 50, 52, 63-67]. One study has reported disruption lasting as long as 5 days post treatment [41].…”

Section: Treatment Safety and Monitoringmentioning

confidence: 99%

Ultrasound enhanced drug delivery to the brain and central nervous system

O’Reilly

Hynynen

2012

International Journal of Hyperthermia

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There is an increasing interest in the use of ultrasound to enhance drug delivery to the brain and central nervous system. Disorders of the brain and CNS historically have had poor response to drug therapy due to the presence of the Blood-Brain barrier (BBB). Techniques for circumventing the BBB are typically highly invasive or involve disrupting large portions of the BBB, exposing the brain to pathogens. Ultrasound can be non-invasively delivered to the brain through the intact skull. When combined with preformed microbubbles, ultrasound can safely induce transient, localized and reversible disruption of the BBB, allowing therapeutics to be delivered. Investigations to date have shown positive response to ultrasound BBB disruption combined with therapeutic agent delivery in rodent models of primary and metastatic brain cancer and Alzheimer’s disease. Recent work in non-human primates has demonstrated that the technique is feasible for use in humans. This review examines the current status of drug delivery to the brain and CNS both by disruption of the BBB, and by ultrasound enhancement of drug delivery through the already compromised BBB. Cellular and physical mechanisms of disruption are discussed, as well as treatment technique, safety and monitoring.

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Effects of combining low frequency ultrasound irradiation with papaverine on the permeability of the blood–tumor barrier

Cited by 13 publications

References 56 publications

Ultrasound-mediated blood–brain barrier disruption for targeted drug delivery in the central nervous system

Ultrasound-mediated blood–brain barrier disruption for targeted drug delivery in the central nervous system

Permeability of the blood–tumor barrier is enhanced by combining vascular endothelial growth factor with papaverine

Ultrasound enhanced drug delivery to the brain and central nervous system

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