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Minimally invasive cutaneous delivery of macromolecules and plasmid DNA via microneedles

Coulman, Sion, Barrow, David Anthony, Anstey, Alexander Vincent, Gateley, Chris, Morrissey, Anthony, Wilke, Nicolle, Allender, Christopher John, Brain, Keith Roger and Birchall, James Caradoc 2006. Minimally invasive cutaneous delivery of macromolecules and plasmid DNA via microneedles. Current drug delivery 3 (1) , pp. 65-75.

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Abstract

The stratum corneum (SC) represents a significant barrier to the delivery of gene therapy formulations. In order to realise the potential of therapeutic cutaneous gene transfer, delivery strategies are required to overcome this exclusion effect. This study investigates the ability of microfabricated silicon microneedle arrays to create micron-sized channels through the SC of ex vivo human skin and the resulting ability of the conduits to facilitate localised delivery of charged macromolecules and plasmid DNA (pDNA). Microscopic studies of microneedle-treated human epidermal membrane revealed the presence of microconduits (10-20 microm diameter). The delivery of a macromolecule, beta-galactosidase, and of a 'non-viral gene vector mimicking' charged fluorescent nanoparticle to the viable epidermis of microneedle-treated tissue was demonstrated using light and fluorescent microscopy. Track etched permeation profiles, generated using 'Franz-type' diffusion cell methodology and a model synthetic membrane showed that >50% of a colloidal particle suspension permeated through membrane pores in approximately 2 hours. On the basis of these results, it is probable that microneedle treatment of the skin surface would facilitate the cutaneous delivery of lipid:polycation:pDNA (LPD) gene vectors, and other related vectors, to the viable epidermis. Preliminary gene expression studies confirmed that naked pDNA can be expressed in excised human skin following microneedle disruption of the SC barrier. The presence of a limited number of microchannels, positive for gene expression, indicates that further studies to optimise the microneedle device morphology, its method of application and the pDNA formulation are warranted to facilitate more reproducible cutaneous gene delivery.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
ISSN: 1567-2018
Last Modified: 04 Jun 2017 01:36
URI: http://orca.cf.ac.uk/id/eprint/891

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