Hydrodynamic gene delivery in human skin using a hollow microneedle device

Dul, M. ORCID: https://orcid.org/0000-0002-0192-2280, Stefanidou, M.., Porta, P., Serve, J., O'Mahony, C., Malissen, B., Henri, S., Levin, Y., Kochba, E., Wong, F.S. ORCID: https://orcid.org/0000-0002-2812-8845, Dayan, C. ORCID: https://orcid.org/0000-0002-6557-3462, Coulman, S.A. ORCID: https://orcid.org/0000-0002-1277-7584 and Birchall, J.C. ORCID: https://orcid.org/0000-0001-8521-6924 2017. Hydrodynamic gene delivery in human skin using a hollow microneedle device. Journal of Controlled Release 265 , pp. 120-131. 10.1016/j.jconrel.2017.02.028

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy Medicine
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Microneedles; Human skin; DNA; Genetic vaccine; Gene therapy; Hydrodynamic
Additional Information:	Released with a Creative Commons Attribution Non-Commercial No Derivatives License (CC BY-NC-ND)
Publisher:	Elsevier
ISSN:	0168-3659
Date of First Compliant Deposit:	20 March 2017
Date of Acceptance:	25 February 2017
Last Modified:	16 Nov 2024 19:00
URI:	https://orca.cardiff.ac.uk/id/eprint/99176

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