Characterisation of cationic amphiphilic cyclodextrins for neuronal delivery of siRNA: effect of reversing primary and secondary face modifications
| dc.contributor.author | O'Mahony, Aoife M. | |
| dc.contributor.author | Doyle, D. | |
| 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 | 2013-01-09T12:08:13Z | |
| dc.date.available | 2013-01-09T12:08:13Z | |
| dc.date.issued | 2012-12-18 | |
| dc.date.updated | 2013-01-04T15:01:51Z | |
| 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.description.status | Peer reviewed | en |
| dc.description.version | Accepted Version | en |
| dc.format.mimetype | application/pdf | en |
| 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. http://dx.doi.org/10.1016/j.ejps.2012.08.020 | en |
| dc.identifier.doi | 10.1016/j.ejps.2012.08.020 | |
| dc.identifier.endpage | 903 | en |
| dc.identifier.issn | 0928-0987 | |
| dc.identifier.issued | 5 | en |
| dc.identifier.journaltitle | European Journal of Pharmaceutical Sciences | en |
| dc.identifier.startpage | 896 | en |
| dc.identifier.uri | https://hdl.handle.net/10468/873 | |
| dc.identifier.volume | 47 | en |
| dc.language.iso | en | en |
| dc.publisher | Elsevier | en |
| dc.rights | © 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] http://dx.doi.org/10.1016/j.ejps.2012.08.020 | en |
| dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | 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 |
