Microneedle delivery of plasmid DNA to living human skin: Formulation coating, skin insertion and gene expression

Pearton, Marc, Saller, Verena, Coulman, Sion ORCID: https://orcid.org/0000-0002-1277-7584, Gateley, Chris, Anstey, Alexander Vincent ORCID: https://orcid.org/0000-0002-6345-4144, Zarnitsyn, Vladimir and Birchall, James Caradoc ORCID: https://orcid.org/0000-0001-8521-6924 2012. Microneedle delivery of plasmid DNA to living human skin: Formulation coating, skin insertion and gene expression. Journal of Controlled Release 160 (3) , pp. 561-569. 10.1016/j.jconrel.2012.04.005

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Abstract

Microneedle delivery of nucleic acids, in particular plasmid DNA (pDNA), to the skin represents a potential new approach for the clinical management of genetic skin diseases and cutaneous cancers, and for intracutaneous genetic immunisation. In this study excised human skin explants were used to investigate and optimise key parameters that will determine stable and effective microneedle-facilitated pDNA delivery. These include (i) high dose-loading of pDNA onto microneedle surfaces, (ii) stability and functionality of the coated pDNA, (iii) skin penetration capability of pDNA-coated microneedles, and (iv) efficient gene expression in human skin. Optimisation of a dip-coating method enabled significant increases in the loading capacity, up to 100 μg of pDNA per 5-microneedle array. Coated microneedles were able to reproducibly perforate human skin at low (< 1 N) insertion forces. The physical stability of the coated pDNA was partially compromised on storage, although this was improved through the addition of saccharide excipients without detriment to the biological functionality of pDNA. The pDNA-coated microneedles facilitated reporter gene expression in viable human skin. The efficiency of gene expression from coated microneedles will depend upon suitable DNA loading, efficient and reproducible skin puncture and rapid in situ dissolution of the plasmid at the site of delivery.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Postgraduate Medical and Dental Education Pharmacy
Subjects:	Q Science > QH Natural history > QH426 Genetics Q Science > QR Microbiology R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Microneedle; Coating; Plasmid DNA; Gene expression; Human skin; Skin puncture
Publisher:	Elsevier
ISSN:	0168-3659
Last Modified:	21 Oct 2022 10:37
URI:	https://orca.cardiff.ac.uk/id/eprint/40823

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