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dc.contributor.authorIslam, Yamir
dc.contributor.authorEhtezazi, Parinaz
dc.contributor.authorCashmore, Andrew
dc.contributor.authorMarinsalda, Elena
dc.contributor.authorLeach, Andrew G.
dc.contributor.authorCoxon, Christopher R.
dc.contributor.authorFatokun, Amos A.
dc.contributor.authorSexton, Darren W.
dc.contributor.authorKhan, Iftikhar
dc.contributor.authorDowning, James
dc.contributor.authorPluchino, Stefano
dc.contributor.authorSivakumaran, Muttuswamy
dc.contributor.authorTeixido, Meritxell
dc.contributor.authorEhtezazi, Touraj
dc.contributor.authorZouganelis, George
dc.date.accessioned2021-01-18T14:29:46Z
dc.date.available2021-01-18T14:29:46Z
dc.date.issued2020-12-14
dc.identifier.citationIslam, Y., Ehtezazi, P., Cashmore, A., Marinsalda, E., Leach, A.G., Coxon, C.R., Fatokun, A.A., Sexton, D.W., Khan, I., Zouganelis, G. and Downing, J., (2020). 'The Inclusion of a Matrix Metalloproteinase-9 Responsive Sequence in Self-assembled Peptide-based Brain-Targeting Nanoparticles Improves the Efficiency of Nanoparticles Crossing the Blood-Brain Barrier at Elevated MMP-9 Levels'. Journal of Pharmaceutical Sciences.en_US
dc.identifier.issn0022-3549
dc.identifier.doi10.1016/j.xphs.2020.12.004
dc.identifier.urihttp://hdl.handle.net/10545/625533
dc.description.abstractThis study investigated whether the inclusion of a matrix metalloproteinase-9 (MMP-9) responsive sequence in self-assembled peptide-based brain-targeting nanoparticles (NPs) would enhance the blood-brain barrier (BBB) penetration when MMP-9 levels are elevated both in the brain and blood circulation. Brain-targeting peptides were conjugated at the N-terminus to MMP-9-responsive peptides, and these were conjugated at the N-terminus to lipid moiety (cholesteryl chloroformate or palmitic acid). Two constructs did not have MMP-9-responsive peptides. NPs were characterised for size, charge, critical micelle concentration, toxicity, blood compatibility, neural cell uptake, release profiles, and in vitro BBB permeability simulating normal or elevated MMP-9 levels. The inclusion of MMP-9-sensitive sequences did not improve the release of a model drug in the presence of active MMP-9 from NPs compared to distilled water. 19F NMR studies suggested the burial of MMP-9-sensitive sequences inside the NPs making them inaccessible to MMP-9. Only cholesterol-GGGCKAPETALC (responsive to MMP-9) NPs showed <5% haemolysis, <1 pg/mL release of IL-1β at 500 μg/mL from THP1 cells, with 70.75 ± 5.78% of NPs crossing the BBB at 24 h in presence of active MMP-9. In conclusion, brain-targeting NPs showed higher transport across the BBB model when MMP-9 levels were elevated and the brain-targeting ligand was responsive to MMP-9.en_US
dc.description.sponsorshipN/Aen_US
dc.language.isoenen_US
dc.publisherElsevier BVen_US
dc.relation.urlhttps://jpharmsci.org/article/S0022-3549(20)30783-8/fulltext#%20en_US
dc.rights.urihttps://www.elsevier.com/tdm/userlicense/1.0/
dc.subjectMMP-9en_US
dc.subjectBrain Drug Deliveryen_US
dc.subjectSelf-Assembled Nanoparticlesen_US
dc.subjectBBB Modelen_US
dc.subjectPeptidesen_US
dc.subjectPersonalised Medicineen_US
dc.titleThe Inclusion of a Matrix Metalloproteinase-9 Responsive Sequence in Self-assembled Peptide-based Brain-Targeting Nanoparticles Improves the Efficiency of Nanoparticles Crossing the Blood-Brain Barrier at Elevated MMP-9 Levelsen_US
dc.typeArticleen_US
dc.contributor.departmentLiverpool John Moores Universityen_US
dc.contributor.departmentUniversity of Manchesteren_US
dc.contributor.departmentHeriot-Watt University, Edinburghen_US
dc.contributor.departmentUniversity of Derbyen_US
dc.contributor.departmentUniversity of Cambridgeen_US
dc.contributor.departmentPeterborough City Hospital, Edith Cavell Campus, Bretton Gate Peterboroughen_US
dc.contributor.departmentBarcelona Institute of Science and Technology, Barcelona, Spainen_US
dc.identifier.journalJournal of Pharmaceutical Scienceen_US
dc.identifier.piiS0022354920307838
dc.source.journaltitleJournal of Pharmaceutical Sciences
dcterms.dateAccepted2020-12-07
refterms.dateFOA2021-01-20T17:37:04Z
dc.author.detail300735en_US


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