Cationic and PEGylated amphiphilic cyclodextrins: co-formulation opportunities for neuronal siRNA delivery

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dc.contributor.authorO'Mahony, Aoife M.
dc.contributor.authorOgier, Julien R.
dc.contributor.authorDarcy, Raphael
dc.contributor.authorCryan, John F.
dc.contributor.authorO'Driscoll, Caitríona M.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Research Council for Science Engineering and Technologyen
dc.contributor.funderIrish Drug Delivery Networken
dc.date.accessioned2016-02-17T11:45:33Z
dc.date.available2016-02-17T11:45:33Z
dc.date.issued2013
dc.description.abstractOptimising non-viral vectors for neuronal siRNA delivery presents a significant challenge. Here, we investigate a co-formulation, consisting of two amphiphilic cyclodextrins (CDs), one cationic and the other PEGylated, which were blended together for siRNA delivery to a neuronal cell culture model. Co-formulated CD-siRNA complexes were characterised in terms of size, charge and morphology. Stability in salt and serum was also examined. Uptake was determined by flow cytometry and toxicity was measured by MTT assay. Knockdown of a luciferase reporter gene was used as a measure of gene silencing efficiency. Incorporation of a PEGylated CD in the formulation had significant effects on the physical and biological properties of CD. siRNA complexes. Co-formulated complexes exhibited a lower surface charge and greater stability in a high salt environment. However, the inclusion of the PEGylated CD also dramatically reduced gene silencing efficiency due to its effects on neuronal uptake. The co-formulation strategy for cationic and PEGylated CDs improved the stability of the CD. siRNA delivery systems, although knockdown efficiency was impaired. Future work will focus on the addition of targeting ligands to the co-formulated complexes to restore transfection capabilities.en
dc.description.sponsorshipScience Foundation Ireland (Grant no. 07/SRC/B1154); Irish Drug Delivery Network; Irish Research Council of Science, Engineering and Technology.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide66413
dc.identifier.citationO’Mahony AM, Ogier J, Darcy R, Cryan JF, O’Driscoll CM (2013) Cationic and PEGylated Amphiphilic Cyclodextrins: Co-Formulation Opportunities for Neuronal Sirna Delivery. PLoS ONE 8(6): e66413. doi:10.1371/journal.pone.0066413en
dc.identifier.doi10.1371/journal.pone.0066413
dc.identifier.issn1932-6203
dc.identifier.issued6en
dc.identifier.journaltitlePLOS ONEen
dc.identifier.urihttps://hdl.handle.net/10468/2374
dc.identifier.volume8en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.rights© 2013 O’Mahony 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 crediteden
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectSmall interfering RNAen
dc.subjectGene deliveryen
dc.subjectIntracellular traffickingen
dc.subjectMammalian neuronsen
dc.subjectNonviral vectorsen
dc.subjectNervous systemen
dc.subjectPlasmid DNAen
dc.subjectNanoparticlesen
dc.subjectTransfectionen
dc.subjectComplexesen
dc.titleCationic and PEGylated amphiphilic cyclodextrins: co-formulation opportunities for neuronal siRNA deliveryen
dc.typeArticle (peer-reviewed)en
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