Gene Delivery into Human Skin In Vitro Using Biphasic Lipid Vesicles

Author(s): Marianna Foldvari, Praveen Kumar, Martin King, Ravinder Batta, Deborah Michel, Ildiko Badea, Mary Wloch.

Journal Name: Current Drug Delivery

Volume 3 , Issue 1 , 2006

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Abstract:

Topical gene delivery to the skin shows great potential for painless, non-invasive administration of novel vaccines and therapeutic agents. The challenge is to develop a pharmaceutically acceptable system that can deliver suitable amounts of plasmid DNA to produce the desired level of response. The purpose of this study was to quantitatively assess DNA delivery by a novel lipid-based biphasic delivery system into the viable layers of excised human skin. Biphasic lipid vesicle formulations, incorporating plasmid DNA were evaluated in vitro in flow-through diffusion cells. Fifty mg DNA formulation containing 10 μg DNA was applied to full-thickness human breast skin for 24 hours. Residual formulation was removed and the skin was washed with PBS, then tape-stripped, followed by DNase treatment to remove surface bound DNA. Skin samples were homogenised and digested overnight with Proteinase K. The resulting supernatant was used as a template for quantitative PCR. Three formulations yielded a significant degree of dermal absorption compared to the controls. Formulation 26-3-2-DNA indicated that approximately 1x10 9 copies of plasmid were absorbed per cm2 skin. Other formulations resulted in 5 x 10 6 copies/cm2 skin (17C3-1-DNA) and 5 x 10 8 copies/cm2 skin (26-3-1- DNA). Biphasic vesicles delivered significant quantities of plasmid DNA into the viable layers of human skin in vitro. The successful delivery of this large (∼ 4, 400 kDa) charged molecule through intact stratum corneum represents a major advance in transdermal macromolecule delivery.

Keywords: Gene delivery, non-viral, lipid vesicles, DNA vaccine

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Article Details

VOLUME: 3
ISSUE: 1
Year: 2006
Page: [89 - 93]
Pages: 5
DOI: 10.2174/156720106775197501

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