Cutaneous DNA delivery and gene expression in ex vivo human skin explants via wet-etch microfabricated microneedles

Birchall, James Caradoc ORCID: https://orcid.org/0000-0001-8521-6924, Coulman, Sion ORCID: https://orcid.org/0000-0002-1277-7584, Pearton, Marc, Allender, Christopher John, Brain, Keith Roger, Anstey, Alexander Vincent ORCID: https://orcid.org/0000-0002-6345-4144, Gateley, Chris, Wilke, Nicolle and Morrissey, Anthony 2005. Cutaneous DNA delivery and gene expression in ex vivo human skin explants via wet-etch microfabricated microneedles. Journal of drug targeting 13 (7) , pp. 415-421. 10.1080/10611860500383705

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Abstract

Microneedle arrays increase skin permeability by forming channels through the outer physical barrier, without stimulating pain receptors populating the underlying dermis. It was postulated that microneedle arrays could facilitate transfer of DNA to human skin epidermis for cutaneous gene therapy applications. Platinum-coated “wet-etch� silicon microneedles were shown to be of appropriate dimensions to create microconduits, approximately 50 μm in diameter, extending through the stratum corneum (SC) and viable epidermis. Following optimisation of skin explant culturing techniques and confirmation of tissue viability, the ability of the microneedles to mediate gene expression was demonstrated using the β-galactosidase reporter gene. Preliminary studies confirmed localised delivery, cellular internalisation and subsequent gene expression of pDNA following microneedle disruption of skin. A combination of this innovative gene delivery platform and the ex vivo skin culture model will be further exploited to optimise cutaneous DNA delivery and address fundamental questions regarding gene expression in skin.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Uncontrolled Keywords:	Microneedles ; human skin ; DNA ; skin organ culture ; ex vivo ; gene expression
Publisher:	Taylor & Francis
ISSN:	1061-186X
Last Modified:	17 Oct 2022 08:44
URI:	https://orca.cardiff.ac.uk/id/eprint/894

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