Mechanistic studies on the uptake and intracellular trafficking of novel cyclodextrin transfection complexes by intestinal epithelial cells

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dc.contributor.author O'Neill, Martin J.
dc.contributor.author Guo, Jianfeng
dc.contributor.author Byrne, Colin
dc.contributor.author Darcy, Raphael
dc.contributor.author O'Driscoll, Caitríona M.
dc.date.accessioned 2013-01-29T10:19:16Z
dc.date.available 2013-01-29T10:19:16Z
dc.date.copyright 2011
dc.date.issued 2011-07
dc.identifier.citation Martin J. O'Neill, Jianfeng Guo, Colin Byrne, Raphael Darcy and Caitriona M. O'Driscoll. (2011) 'Mechanistic studies on the uptake and intracellular trafficking of novel cyclodextrin transfection complexes by intestinal epithelial cells'. International Journal of Pharmaceutics, 413 (1-2):174-183. en
dc.identifier.volume 413 en
dc.identifier.issued 1-2 en
dc.identifier.startpage 174 en
dc.identifier.endpage 183 en
dc.identifier.issn 0378-5173
dc.identifier.uri http://hdl.handle.net/10468/935
dc.identifier.doi 10.1016/j.ijpharm.2011.04.021
dc.description.abstract Oral delivery of gene therapeutics would facilitate treatment of local intestinal disease, including colon cancer and inflammatory bowel disease, thus avoiding invasive surgery. The aims of this study were to investigate; if the orientation of the lipid tail on the cyclodextrin (CD) influenced the efficacy of a novel poly-6-cationic amphiphilic CD to transfect intestinal enterocytes; the endocytotic uptake pathway(s), and, the intracellular trafficking of the CD.DNA complexes. Inhibitors of clathrin- and caveolae- mediated endocytosis and macropinocytosis were used to determine the mechanism(s) of CD.DNA uptake by both undifferentiated and differentiated Caco-2 cells. Cell surface heparan sulphate proteoglycans were involved in the association of CD.DNA complexes with undifferentiated Caco-2 cells. Complexation of pDNA with CD facilitated significant levels of pDNA uptake and gene expression (comparable to PEI) in both undifferentiated and differentiated Caco-2 cells. Disruption of intracellular vesicular trafficking reduced transfection activity. CD was also capable of transfecting the more physiologically relevant differentiated Caco-2 model. Macropinocytosis was responsible for the uptake of CD.DNA transfection complexes by both undifferentiated and differentiated Caco-2 cells. The ability of this novel CD to transfect differentiated intestinal cells indicates the potential of this vector for oral gene delivery. en
dc.description.sponsorship Science Foundation Ireland (Strategic Research Cluster and the Irish Drug Delivery Network); Enterprise Ireland (via commercial fund technology development); 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.relation.uri http://www.sciencedirect.com/science/article/pii/S0378517311003279
dc.rights Copyright © 2011, Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in International Journal of Pharmaceutics . 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 International Journal of Pharmaceutics [413, 1-2, 15 July 2011] DOI: http://dx.doi.org/10.1016/j.ijpharm.2011.04.021 en
dc.subject Non-viral gene therapy en
dc.subject Cyclodextrins en
dc.subject Intestinal delivery en
dc.subject Uptake pathways en
dc.subject Intracellular trafficking en
dc.subject.lcsh Gene Therapy--methods en
dc.title Mechanistic studies on the uptake and intracellular trafficking of novel cyclodextrin transfection complexes by intestinal epithelial cells en
dc.type Article (peer-reviewed) en
dc.internal.authorurl http://publish.ucc.ie/researchprofiles/C019/caitrionaodriscoll en
dc.internal.authorcontactother Caitriona O'Driscoll, School Of Pharmacy, University College Cork, Cork, Ireland. +353-21-490-3000 Email: caitriona.odriscoll@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2013-01-17T15:16:15Z
dc.description.version Accepted Version en
dc.internal.rssid 99145988
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Enterprise Ireland en
dc.contributor.funder Irish Research Council for Science Engineering and Technology en
dc.description.status Peer reviewed en
dc.identifier.journaltitle International Journal of Pharmaceutics en
dc.internal.copyrightchecked No - CORA - ROMEO - Elsevier. Accepted Version and set statement. en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress caitriona.odriscoll@ucc.ie en


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