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Brain-Targeted Delivery of Pre-miR-29b Using Lactoferrin-Stearic Acid-Modified-Chitosan/Polyethyleneimine Polyplexes

2020Journal article Open access
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dc.contributor.authorPereira, Patrícia
dc.contributor.authorBarreira, Maria
dc.contributor.authorCruz, Carla
dc.contributor.authorTomás, Joana
dc.contributor.authorLuís, Ângelo
dc.contributor.authorPedro, Augusto
dc.contributor.authorQueiroz, João
dc.contributor.authorSousa, Fani
dc.date.accessioned2020-12-02T10:21:14Z
dc.date.available2020-12-02T10:21:14Z
dc.date.issued2020
dc.description.abstractThe efficacy of brain therapeutics is largely hampered by the presence of the blood-brain barrier (BBB), mainly due to the failure of most (bio) pharmaceuticals to cross it. Accordingly, this study aims to develop nanocarriers for targeted delivery of recombinant precursor microRNA (pre-miR-29b), foreseeing a decrease in the expression of the BACE1 protein, with potential implications in Alzheimer's disease (AD) treatment. Stearic acid (SA) and lactoferrin (Lf) were successfully exploited as brain-targeting ligands to modify cationic polymers (chitosan (CS) or polyethyleneimine (PEI)), and its BBB penetration behavior was evaluated. The intracellular uptake of the dual-targeting drug delivery systems by neuronal cell models, as well as the gene silencing efficiency of recombinant pre-miR-29b, was analyzed in vitro. Labeled pre-miR-29b-CS/PEI-SA-Lf systems showed very strong fluorescence in the cytoplasm and nucleus of RBE4 cells, being verified the delivery of pre-miR-29b to neuronal cells after 1 h transfection. The experiment of transport across the BBB showed that CS-SA-Lf delivered 65% of recombinant pre-miR-29b in a period of 4 h, a significantly higher transport ratio than the 42% found for PEI-SA-Lf in the same time frame. Overall, a novel procedure for the dual targeting of DDS is disclosed, opening new perspectives in nanomedicines delivery, whereby a novel drug delivery system harvests the merits and properties of the different immobilized ligands.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3390/ph13100314pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/10530
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationCICECO-Aveiro Institute of Materials
dc.relationCICECO-Aveiro Institute of Materials
dc.relationCentre for Mechanical Enginnering, Materials and Processes
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectBlood-brain barrierpt_PT
dc.subjectChitosanpt_PT
dc.subjectDrug delivery systempt_PT
dc.subjectLactoferrinpt_PT
dc.subjectPolyethyleneiminept_PT
dc.subjectRecombinant miRNApt_PT
dc.titleBrain-Targeted Delivery of Pre-miR-29b Using Lactoferrin-Stearic Acid-Modified-Chitosan/Polyethyleneimine Polyplexespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCICECO-Aveiro Institute of Materials
oaire.awardTitleCICECO-Aveiro Institute of Materials
oaire.awardTitleCentre for Mechanical Enginnering, Materials and Processes
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/PEst-OE%2FSAU%2FUI0709%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50011%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50011%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00285%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FBII-BBF%2F29496%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F81914%2F2011/PT
oaire.citation.issue10pt_PT
oaire.citation.startPage314pt_PT
oaire.citation.titlePharmaceuticalspt_PT
oaire.citation.volume13pt_PT
oaire.fundingStream5876
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream9471 - RIDTI
oaire.fundingStreamSFRH
person.familyNamePereira
person.familyNameCruz
person.familyNameMelfe Tomás
person.familyNameSantos Luís
person.familyNameQuaresma Henriques Pedro
person.familyNameQueiroz
person.familyNameSousa
person.givenNamePatrícia
person.givenNameCarla
person.givenNameJoana Filipa
person.givenNameÂngelo Filipe
person.givenNameAugusto
person.givenNameJoão
person.givenNameFani
person.identifierhttps://scholar.google.com/citations?user=oer44UoAAAAJ&hl=pt-PT&oi=ao
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person.identifier.orcid0000-0002-5665-5271
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person.identifier.orcid0000-0003-0712-6522
person.identifier.orcid0000-0001-8194-6022
person.identifier.orcid0000-0002-3096-8325
person.identifier.orcid0000-0001-9996-2194
person.identifier.ridI-7806-2013
person.identifier.ridL-3104-2014
person.identifier.ridA-2014-2017
person.identifier.scopus-author-id56111844900
person.identifier.scopus-author-id7202701394
person.identifier.scopus-author-id54080426100
person.identifier.scopus-author-id7003705645
person.identifier.scopus-author-id7005110268
project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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