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dc.contributor.authorBaghirov, Habib
dc.contributor.authorSnipstad, Sofie
dc.contributor.authorSulheim, Einar
dc.contributor.authorBerg, Sigrid
dc.contributor.authorHansen, Rune
dc.contributor.authorThorsen, Frits
dc.contributor.authorMørch, Ýrr Asbjørg
dc.contributor.authorDavies, Catharina de Lange
dc.contributor.authorÅslund, Andreas
dc.date.accessioned2018-12-20T08:39:14Z
dc.date.available2018-12-20T08:39:14Z
dc.date.issued2018
dc.identifier.citationPLoS ONE, 2018, 13 (1), e091102, pp 18nb_NO
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11250/2578426
dc.description.abstractThe treatment of brain diseases is hindered by the blood-brain barrier (BBB) preventing most drugs from entering the brain. Focused ultrasound (FUS) with microbubbles can open the BBB safely and reversibly. Systemic drug injection might induce toxicity, but encapsulation into nanoparticles reduces accumulation in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a melanoma brain metastasis model. With a dual-frequency ultrasound transducer generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle-microbubbles and low-frequency FUS, and applied high-frequency FUS to generate acoustic radiation force and push nanoparticles through the extracellular matrix. Using confocal microscopy and image analysis, we quantified nanoparticle extravasation and distribution in the brain parenchyma. We also evaluated haemorrhage, as well as the expression of P-glycoprotein, a key BBB component. FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the distribution depended on the extent of BBB opening. The results from acoustic radiation force were not conclusive, but in a few animals some effect could be detected. P-glycoprotein was not significantly altered immediately after sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can achieve accumulation and displacement of nanoparticles in the brain parenchyma.nb_NO
dc.language.isoengnb_NO
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleUltrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour modelnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.pagenumberart. e091102, pp 18nb_NO
dc.source.volume13nb_NO
dc.source.journalPLoS ONEnb_NO
dc.source.issue1nb_NO
dc.relation.projectNorges forskningsråd: 220005nb_NO
dc.relation.projectNorges forskningsråd: 220005nb_NO
dc.relation.projectNorges forskningsråd: 226159nb_NO


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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal