Journal
JOURNAL OF DRUG TARGETING
Volume 13, Issue 7, Pages 415-421Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10611860500383705
Keywords
microneedles; human skin; DNA; skin organ culture; ex vivo; gene expression
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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 mu m 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 beta-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.
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