Hydrodynamic gene delivery in human skin using a hollow microneedle device

Simple item page
dc.check.date2018-02-28
dc.check.infoAccess to this article is restricted for 12 months after publication by request of the publisher.en
dc.contributor.authorDul, M.
dc.contributor.authorStefanidou, M.
dc.contributor.authorPorta, P.
dc.contributor.authorServe, J.
dc.contributor.authorO'Mahony, Conor
dc.contributor.authorMalissen, B.
dc.contributor.authorHenri, S.
dc.contributor.authorLevin, Y.
dc.contributor.authorKochba, E.
dc.contributor.authorWong, F. S.
dc.contributor.authorDayan, C.
dc.contributor.authorCoulman, S. A.
dc.contributor.authorBirchall, J. C.
dc.contributor.funderSeventh Framework Programmeen
dc.date.accessioned2017-10-20T09:00:30Z
dc.date.available2017-10-20T09:00:30Z
dc.date.issued2017-02-28
dc.date.updated2017-09-22T11:56:21Z
dc.description.abstractMicroneedle 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.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDul, 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.2017.02.028en
dc.identifier.doi10.1016/j.jconrel.2017.02.028
dc.identifier.issn0168-3659
dc.identifier.journaltitleJournal of Controlled Releaseen
dc.identifier.urihttps://hdl.handle.net/10468/4919
dc.language.isoenen
dc.publisherElsevier B. V.en
dc.relation.projectinfo: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-ASIen
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.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectMicroneedlesen
dc.subjectHuman skinen
dc.subjectDNAen
dc.subjectGenetic vaccineen
dc.subjectGene therapyen
dc.subjectHydrodynamicen
dc.titleHydrodynamic gene delivery in human skin using a hollow microneedle deviceen
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
2649.pdf
Size:
2.45 MB
Format:
Adobe Portable Document Format
Description:
Accepted Version
Download
Thumbnail Image
Name:
1-s2.0-S0168365917300871-mmc1.pptx
Size:
61.6 MB
Format:
Microsoft Powerpoint XML
Description:
Supplementary Data
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Tyndall National Institute - Journal Articles