Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model

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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, Yrr
dc.contributor.authorde Lange Davies, Catharina
dc.contributor.authorÅslund, Andreas K. O.
dc.contributor.funderHelse Midt-Norge
dc.contributor.funderNorges Forskningsråd
dc.date.accessioned2018-02-20T13:24:11Z
dc.date.available2018-02-20T13:24:11Z
dc.date.issued2018
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 con focal 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.en
dc.description.sponsorshipNorges Forskningsråd (NANO2021 (220005); FRIMEDBIO (240316); BIOTEK2021(226159)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide0191102
dc.identifier.citationBaghirov, H., Snipstad, S., Sulheim, E., Berg, S., Hansen, R., Thorsen, F., Mørch, Y., de Lange Davies, C. and Åslund, A. K. O. (2018) 'Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model', PLOS ONE, 13(1), e0191102 (18pp). doi: 10.1371/journal.pone.0191102en
dc.identifier.doi10.1371/journal.pone.0191102
dc.identifier.endpage18
dc.identifier.issn1932-6203
dc.identifier.issued1
dc.identifier.journaltitlePLOS ONEen
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/5491
dc.identifier.volume13
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.relation.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191102
dc.rights© 2018, Baghirov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectFocused ultrasounden
dc.subjectDrug deliveryen
dc.subjectStabilized microbubblesen
dc.subjectImage analysisen
dc.subjectBlooden
dc.subjectBarrieren
dc.subjectDisruptionen
dc.subjectPermeabilityen
dc.subjectMechanismen
dc.subjectDiscoveryen
dc.titleUltrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour modelen
dc.typeArticle (peer-reviewed)en
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