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

Show simple item record

dc.contributor.author O'Mahony, Aoife M.
dc.contributor.author Ogier, Julien R.
dc.contributor.author Darcy, Raphael
dc.contributor.author Cryan, John F.
dc.contributor.author O'Driscoll, Caitríona M.
dc.date.accessioned 2016-02-17T11:45:33Z
dc.date.available 2016-02-17T11:45:33Z
dc.date.issued 2013
dc.identifier.citation O’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.0066413 en
dc.identifier.volume 8 en
dc.identifier.issued 6 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/2374
dc.identifier.doi 10.1371/journal.pone.0066413
dc.description.abstract Optimising 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.sponsorship Science Foundation Ireland (Grant no. 07/SRC/B1154); Irish Drug Delivery Network; Irish Research Council of Science, Engineering and Technology. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Public Library of Science en
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 credited en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Small interfering RNA en
dc.subject Gene delivery en
dc.subject Intracellular trafficking en
dc.subject Mammalian neurons en
dc.subject Nonviral vectors en
dc.subject Nervous system en
dc.subject Plasmid DNA en
dc.subject Nanoparticles en
dc.subject Transfection en
dc.subject Complexes en
dc.title Cationic and PEGylated amphiphilic cyclodextrins: co-formulation opportunities for neuronal siRNA delivery en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Caitríona M. O'Driscoll, University College Cork, Cork, Ireland. +353-21-490-3000 Email: caitriona.odriscoll@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.wokid WOS:000320846500048
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Irish Research Council for Science Engineering and Technology en
dc.contributor.funder Irish Drug Delivery Network en
dc.description.status Peer reviewed en
dc.identifier.journaltitle PLOS ONE en
dc.internal.IRISemailaddress caitriona.odriscoll@ucc.ie en
dc.identifier.articleid e66413


Files in this item

This item appears in the following Collection(s)

Show simple item record

© 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 credited Except where otherwise noted, this item's license is described as © 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 credited
This website uses cookies. By using this website, you consent to the use of cookies in accordance with the UCC Privacy and Cookies Statement. For more information about cookies and how you can disable them, visit our Privacy and Cookies statement