Characterisation of cationic amphiphilic cyclodextrins for neuronal delivery of siRNA: effect of reversing primary and secondary face modifications

Show simple item record O'Mahony, Aoife M. Doyle, D. Darcy, Raphael Cryan, John F. O'Driscoll, Caitríona M. 2013-01-09T12:08:13Z 2013-01-09T12:08:13Z 2012-12-18
dc.identifier.citation O'Mahony A.M., Doyle D., Darcy R., Cryan J.F., O'Driscoll C.M. (2012) 'Characterisation of cationic amphiphilic cyclodextrins for neuronal delivery of siRNA: Effect of reversing primary and secondary face modifications'. European Journal of Pharmaceutical Sciences, 47(5), pp. 896–903. en
dc.identifier.volume 47 en
dc.identifier.issued 5 en
dc.identifier.startpage 896 en
dc.identifier.endpage 903 en
dc.identifier.issn 0928-0987
dc.identifier.doi 10.1016/j.ejps.2012.08.020
dc.description.abstract Significant research is focused on the development of non-viral vectors for delivery of siRNA to neurons and the central nervous system. Cyclodextrins (CDs) have shown great promise as efficient and low toxicity gene delivery vectors in various cell types. Here, we investigate two CDs for siRNA delivery in a neuronal cell model. These CDs were substituted on opposite faces (primary and secondary) with amphiphilic and cationic groups. Physical properties of CD.siRNA complexes, including size, charge and stability were measured. In vitro investigations were carried out in immortalised hypothalamic neurons. Neuronal cell uptake was measured by flow cytometry and cytotoxicity was assessed by MTT assay. Knockdown of a luciferase reporter gene was used as a measure of gene silencing efficiency. Both CDs interacted with siRNA, yielding nanosized cationic complexes which exhibited good stability on storage. A favourable toxicity profile was demonstrated for the CD.siRNA complexes. However, only one of the two CDs mediated high levels of neuronal uptake and efficient gene silencing, equivalent to those achieved with a commercial lipid-based vector. Despite the suitability of both CDs as siRNA delivery vectors in terms of their ability to complex siRNA and the properties of the complexes yielded, only one CD achieved good transfection efficiency. This was likely due to the differences in their chemical structures. The effective CD offers great potential as a novel non-toxic vector for neuronal siRNA delivery. en
dc.description.sponsorship Science Foundation Ireland(Grant no. 07/SRC/B1154); Irish Research Council for Science Engineering and Technology (Embark initiative) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier en
dc.rights Copyright © 2012, Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Pharmaceutical Sciences. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in European Journal of Pharmaceutical Sciences, [47, 18 December 2012] en
dc.subject Modified cyclodextrins en
dc.subject siRNA delivery en
dc.subject Neurons en
dc.subject Low-toxicity en
dc.subject.lcsh Cyclodextrins en
dc.title Characterisation of cationic amphiphilic cyclodextrins for neuronal delivery of siRNA: effect of reversing primary and secondary face modifications en
dc.type Article (peer-reviewed) en
dc.internal.authorurl en
dc.internal.authorcontactother Caitriona O'Driscoll, School Of Pharmacy, University College Cork, Cork, Ireland. +353-21-490-3000 Email: en
dc.internal.availability Full text available en 2013-01-04T15:01:51Z
dc.description.version Accepted Version en
dc.internal.rssid 181751479
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 European Journal of Pharmaceutical Sciences en
dc.internal.copyrightchecked Yes. CORA - RoMEO. en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress en

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