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.author Baghirov, Habib
dc.contributor.author Snipstad, Sofie
dc.contributor.author Sulheim, Einar
dc.contributor.author Berg, Sigrid
dc.contributor.author Hansen, Rune
dc.contributor.author Thorsen, Frits
dc.contributor.author Mørch, Yrr
dc.contributor.author de Lange Davies, Catharina
dc.contributor.author Åslund, Andreas K. O.
dc.date.accessioned 2018-02-20T13:24:11Z
dc.date.available 2018-02-20T13:24:11Z
dc.date.issued 2018
dc.identifier.citation Baghirov, 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.0191102 en
dc.identifier.volume 13
dc.identifier.issued 1
dc.identifier.startpage 1
dc.identifier.endpage 18
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/5491
dc.identifier.doi 10.1371/journal.pone.0191102
dc.description.abstract The 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.sponsorship Norges Forskningsråd (NANO2021 (220005); FRIMEDBIO (240316); BIOTEK2021(226159) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Public Library of Science en
dc.relation.uri http://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.uri https://creativecommons.org/licenses/by/4.0/
dc.subject Focused ultrasound en
dc.subject Drug delivery en
dc.subject Stabilized microbubbles en
dc.subject Image analysis en
dc.subject Blood en
dc.subject Barrier en
dc.subject Disruption en
dc.subject Permeability en
dc.subject Mechanism en
dc.subject Discovery en
dc.title Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Habib Baghirov, Pharmacy, University College Cork, Cork, Ireland. +353-21-490-3000 Email: habib.baghirov@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.wokid WOS:000414769900030
dc.contributor.funder Helse Midt-Norge
dc.contributor.funder Norges Forskningsråd
dc.description.status Peer reviewed en
dc.identifier.journaltitle PLOS ONE en
dc.internal.IRISemailaddress habib.baghirov@ucc.ie en
dc.identifier.articleid e0191102


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© 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. Except where otherwise noted, this item's license is described as © 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.
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