Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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 and Mary Wloch

Volume 3, Issue 1, 2006

Page: [89 - 93] Pages: 5

DOI: 10.2174/156720106775197501

Price: $65

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

« Previous

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy