Cutaneous gene expression of plasmid DNA in excised human skin following delivery via microchannels created by radio frequency ablation

• Published in: International journal of pharmaceutics Vol. 312; no. 1; pp. 15 - 23
• Main Authors: Birchall, James, Coulman, Sion, Anstey, Alexander, Gateley, Chris, Sweetland, Helen, Gershonowitz, Amikam, Neville, Lewis, Levin, Galit
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 07.04.2006; Elsevier
• Subjects: Administration, Cutaneous; Aged; beta-Galactosidase - biosynthesis; beta-Galactosidase - genetics; Biological and medical sciences; Catheter Ablation; DNA - administration & dosage; Electricity; Electrodes; Female; Gene Expression; Gene therapy; General pharmacology; Genes, Reporter; Humans; In Vitro Techniques; Medical sciences; Middle Aged; Nanostructures; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasmid DNA; Plasmids; Radiofrequency ablation; Radiofrequency-microchannels; Skin; Skin - metabolism; Radiofrequency ablation; Skin; Plasmid DNA; Gene therapy; Radiofrequency-microchannels; Human; Plasmid; Pharmaceutical technology; DNA; Gene expression; Percutaneous route
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2005.12.036

The skin is a valuable organ for the development and exploitation of gene medicines. Delivering genes to skin is restricted however by the physico-chemical properties of DNA and the stratum corneum (SC) barrier. In this study, we demonstrate the utility of an innovative technology that creates transient microconduits in human skin, allowing DNA delivery and resultant gene expression within the epidermis and dermis layers. The radio frequency (RF)-generated microchannels were of sufficient morphology and depth to permit the epidermal delivery of 100 nm diameter nanoparticles. Model fluorescent nanoparticles were used to confirm the capacity of the channels for augmenting diffusion of macromolecules through the SC. An ex vivo human organ culture model was used to establish the gene expression efficiency of a β-galactosidase reporter plasmid DNA applied to ViaDerm™ treated skin. Skin treated with ViaDerm™ using 50 μm electrode arrays promoted intense levels of gene expression in the viable epidermis. The intensity and extent of gene expression was superior when ViaDerm™ was used following a prior surface application of the DNA formulation. In conclusion, the RF-microchannel generator (ViaDerm™) creates microchannels amenable for delivery of nanoparticles and gene therapy vectors to the viable region of skin.