Article

Electro-gene transfer to skin using a noninvasive multielectrode array.

Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, 23508, USA.
Journal of Controlled Release (Impact Factor: 7.63). 05/2011; 151(3):256-62. DOI: 10.1016/j.jconrel.2011.01.014
Source: PubMed

ABSTRACT Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection of plasmid DNA alone over 15 days. Furthermore, gene expression could be enhanced by increasing the size of the treatment area. Transgene-expressing cells were observed exclusively in the epidermal layer of the skin. In contrast to caliper or plate electrodes, skin EP with the MEA greatly reduced muscle twitching and resulted in minimal and completely recoverable skin damage. These results suggest that EP with MEA can be an efficient and non-invasive skin delivery method with less adverse side effects than other EP delivery systems and promising clinical applications.

0 Bookmarks
 · 
150 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Therapeutic delivery of angiogenic growth factors is a promising approach for treating ischemia observed in skin flaps and chronic wounds. Several studies have demonstrated that vascular endothelial growth factor (VEGF) helps mitigate skin flap necrosis by facilitating angiogenesis. The present study aimed to demonstrate an electrically-mediated nonviral gene delivery approach using a non-invasive multi-electrode array (MEA) for effective treatment of ischemic skin flaps.
    The Journal of Gene Medicine 05/2014; 16(3-4):55-65. DOI:10.1002/jgm.2759 · 1.95 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Electroporation can be used as a tool for extracting or introducing molecules from or into a cell. The most important and promising applications of electroporation in medicine and biotechnology are described.
    IEEE Electrical Insulation Magazine 01/2013; 29(1):29-37. DOI:10.1109/MEI.2013.6410537 · 1.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the present study, we designed and developed novel lipids that include (Z)-1-(Octadec-9-en-1-yl)-pyrrolidine (Cy5T), 1, 1-Di-((Z)-octadec-9-en-1-yl)pyrrolidin-1-ium iodide (Cy5), (Z)-1-(Octadec-9-en-1-yl)-piperidine (Cy6T), and 1, 1-Di-((Z)-octadec-9-en-1-yl) piperidin-1-ium iodide (Cy6) to enhance the transdermal permeation of some selected drugs. Firstly, we evaluated the transdermal permeation efficacies of these lipids as chemical permeation enhancers in vehicle formulations for melatonin, ß-estradiol, caffeine, α-MSH, and spantide using franz diffusion cells. Among them Cy5 lipid was determined to be the most efficient by increasing the transdermal permeation of melatonin, ß-estradiol, caffeine, α-MSH, and spantide by 1.5 to 3.26-fold more at the epidermal layer and 1.3 to 2.5-fold more at the dermal layer, in comparison to either NMP or OA. Hence we developed a nanoparticle system (cy5 lipid ethanol drug nanoparticles) to evaluate any further improvement in the drug penetration. Cy5 lipid formed uniformly sized nanoparticles ranging from 150-200 nm depending on the type of drug. Further, Cy5 based nanoparticle system significantly (p<0.05) increased the permeation of all the drugs in comparison to the lipid solution and standard permeation enhancers. There were about 1.54 to 22-fold more of drug retained in the dermis for the Cy5 based nanoparticles compared to OA/NMP standard enhancers and 3.87 to 66.67-fold more than lipid solution. In addition, epifluorescent microscopic analysis in rhodamine-PE permeation studies confirmed the superior permeation enhancement of LEDs (detection of fluorescence up to skin depth of 340 μm) more than lipid solution, which revealed fluorescence up to skin depth of only 260 μm. In summary the present findings demonstrate that i) cationic lipid with 5 membered amine heterocyclic ring has higher permeating efficacy than the 6 membered amine hertocyclic ring. ii) The nanoparticle system prepared with Cy5 showed significant (p<0.05) increase in the permeation of the drugs than the control penetration enhancers, oleic acid and NMP.
    PLoS ONE 12/2013; 8(12):e82581. DOI:10.1371/journal.pone.0082581 · 3.53 Impact Factor
    This article is viewable in ResearchGate's enriched format

Full-text

Download
85 Downloads
Available from
May 23, 2014