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Gene delivery to human skin using microneedle arrays

Coulman, Sion Andrew 2006. Gene delivery to human skin using microneedle arrays. PhD Thesis, Cardiff University.

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Abstract

Cutaneous delivery of macromolecules is significantly impeded by the inherent barrier properties of the stratum corneum (SC). Within the last decade sophisticated engineering techniques have enabled the manufacture of microneedle arrays. These are innovative devices consisting of micron-sized needles which when inserted into the skin create physical conduits across the SC but do not impinge upon underlying nerve fibres or blood vessels. This study assessed the ability of microfabricated silicon microneedle arrays to penetrate the SC of ex vivo human skin for the localised delivery and subsequent expression of non-viral gene therapy formulations. Cutaneous gene therapy may represent a new method for the treatment of, or vaccination against, a range of candidate diseases. Microneedle arrays of variant geometries and morphologies, created using dry- and wet-etch microfabrication methods, were characterised by scanning electron microscopy. The potential of these devices for the cutaneous delivery of gene therapy formulations was initially demonstrated by permeation of a size and surface representative fluorescent nanoparticle across microneedle treated human epidermal membrane and observation of these nanoparticles in micron-sized conduits created in excised human skin. The ability to express exogenous genes within ex vivo human skin was subsequently proven by intradermal injection of the pCMVp reporter plasmid. However, a non-viral gene therapy vector failed to enhance cutaneous transfection. Cutaneous plasmid DNA delivery using the microneedle device facilitated effective, if somewhat limited and irreproducible, transfection of epidermal cells proximal to microchannels created in the skin. These investigations confirmed the ability of a silicon microneedle device to deliver macromolecular formulations, including plasmid DNA, to the viable epidermis and have demonstrated exogenous gene expression within human skin. However, limited and unpredictable gene expression following microneedle mediated delivery indicate that further studies to optimise the microneedle array morphology, its method of application and the plasmid DNA formulation are warranted.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Pharmacy
Subjects: R Medicine > RS Pharmacy and materia medica
ISBN: 9781303173943
Date of First Compliant Deposit: 30 March 2016
Last Modified: 10 Jan 2018 00:35
URI: http://orca-mwe.cf.ac.uk/id/eprint/54257

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