Gene expression in an intact ex-vivo skin tissue model following percutaneous delivery of cationic liposome-plasmid DNA complexes

Birchall, James Caradoc ORCID: https://orcid.org/0000-0001-8521-6924, Marichal, C., Campbell, L., Alwan, A., Hadgraft, J. and Gumbleton, Mark ORCID: https://orcid.org/0000-0002-7386-311X 2000. Gene expression in an intact ex-vivo skin tissue model following percutaneous delivery of cationic liposome-plasmid DNA complexes. International Journal of Pharmaceutics 197 (1-2) , pp. 233-238. 10.1016/S0378-5173(00)00336-7

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Abstract

The skin represents an attractive site for the localised gene therapy of dermatological pathologies and as a potential antigen bioreactor following transdermal delivery. Potential also exists for the gene therapy of skin as a cosmetic intervention. The most exploited non-viral genedelivery system involves the complexation of cationic liposomes with plasmidDNA (pDNA) to form lipid:pDNA vectors that protect the DNA from nuclease-mediated degradation and improve transgene-cell interactions. Despite numerous studies examining the potential for these vectors in delivering genes to a variety of keratinocyte models, investigations into the topical application of such complexes to intactskintissue is limited. This ex-vivo study, conducted with intactskintissue derived from hairless mice, provides quantitative confirmation that topical administration of cationic lipid:pDNA complexes can mediate uptake and expression of reporter pDNA (33-fold higher compared with control) in viable epidermal tissue. The ex-vivo study design provides for intactskintissue that has not been subjected to depilatory procedures of potential detriment to stratum corneum barrier function, and can be utilised for the quantitative and efficient examination of a potentially wide range of non-viral gene vectors designed for epidermal expression.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	Skin; Gene therapy; Exvivomodel; Cationic liposomes; Epidermis
Publisher:	Elsevier
ISSN:	0378-5173
Last Modified:	20 Oct 2022 09:31
URI:	https://orca.cardiff.ac.uk/id/eprint/32361

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