Hydrodynamic gene delivery in human skin using a hollow microneedle device

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dc.contributor.author Dul, M.
dc.contributor.author Stefanidou, M.
dc.contributor.author Porta, P.
dc.contributor.author Serve, J.
dc.contributor.author O'Mahony, Conor
dc.contributor.author Malissen, B.
dc.contributor.author Henri, S.
dc.contributor.author Levin, Y.
dc.contributor.author Kochba, E.
dc.contributor.author Wong, F. S.
dc.contributor.author Dayan, C.
dc.contributor.author Coulman, S. A.
dc.contributor.author Birchall, J. C.
dc.date.accessioned 2017-10-20T09:00:30Z
dc.date.available 2017-10-20T09:00:30Z
dc.date.issued 2017-02-28
dc.identifier.citation Dul, M., Stefanidou, M., Porta, P., Serve, J., O'Mahony, C., Malissen, B., Henri, S., Levin, Y., Kochba, E., Wong, F. S., Dayan, C., Coulman, S. A. and Birchall, J. C. (2017) 'Hydrodynamic gene delivery in human skin using a hollow microneedle device', Journal of Controlled Release. doi:10.1016/j.jconrel.2017.02.028 en
dc.identifier.issn 0168-3659
dc.identifier.uri http://hdl.handle.net/10468/4919
dc.identifier.doi 10.1016/j.jconrel.2017.02.028
dc.description.abstract Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50 μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier B. V. en
dc.rights © 2017, Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 licence. en
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject Microneedles en
dc.subject Human skin en
dc.subject DNA en
dc.subject Genetic vaccine en
dc.subject Gene therapy en
dc.subject Hydrodynamic en
dc.title Hydrodynamic gene delivery in human skin using a hollow microneedle device en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Conor O'Mahony, Tyndall Microsystems, University College Cork, Cork, Ireland. +353-21-490-3000 Email: conor.omahony@tyndall.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted for 12 months after publication by request of the publisher. en
dc.check.date 2018-02-28
dc.date.updated 2017-09-22T11:56:21Z
dc.description.version Accepted Version en
dc.internal.rssid 407848165
dc.contributor.funder Seventh Framework Programme en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Journal of Controlled Release en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress conor.omahony@tyndall.ie en
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP1::HEALTH/305305/EU/Beta cell preservation via antigen-specific immunotherapy in Type 1 Diabetes: Enhanced Epidermal Antigen Delivery Systems./EE-ASI en

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© 2017, Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 licence. Except where otherwise noted, this item's license is described as © 2017, Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 licence.
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