Cationic and PEGylated amphiphilic cyclodextrins: co-formulation opportunities for neuronal siRNA delivery
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.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.date.accessioned | 2016-02-17T11:45:33Z | |
dc.date.available | 2016-02-17T11:45:33Z | |
dc.date.issued | 2013 | |
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.description.status | Peer reviewed | en |
dc.description.version | Published Version | en |
dc.format.mimetype | application/pdf | en |
dc.identifier.articleid | e66413 | |
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.doi | 10.1371/journal.pone.0066413 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.issued | 6 | en |
dc.identifier.journaltitle | PLOS ONE | en |
dc.identifier.uri | https://hdl.handle.net/10468/2374 | |
dc.identifier.volume | 8 | 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 |
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