Gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal delivery of interleukin-4 using ultradeformable cationic liposome

J Gene Med. 2010 Jun;12(6):481-90. doi: 10.1002/jgm.1459.

Abstract

Background: Topical transdermal gene delivery to the skin shows great potential for painless, non-invasive administration of vaccines and therapeutic agents. Interleukin (IL)-4 strategies have shown a good antipsoriatic effect in clinic trials. To date, no information has been acquired on the effectiveness of gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal penetration of murine IL-4 (mIL-4) using ultradeformable cationic liposome (UCL).

Methods: In the present study, we synthesized an UCL and determined a suitable formula for transdermally delivering plasmid DNA to mouse skin. We then tested the antipsoriatic efficacy in the K14-VEGF transgenic mouse model by transdermal delivery of mIL-4 using UCL.

Results: We found that plasmid DNA was transdermally delivered to vicinal sites of epidermis and hair follicles using this optimized formula. Plasmid DNA expression was detected in ear skin. Twenty-four hours after topical application, plasmid DNA was not detected in blood serum and liver, which may decrease the risk of insertion of promoter from plasmid to genomic DNA. Mice treated with UCL/mIL-4 displayed a mild psoriasis phenotype. Histological analysis of pathological score using the Baker scoring system revealed an antipsoriatic effect. Immunohistochemical analysis revealed that hyperplastic and inflamed vessels were suppressed.

Conclusions: These observations provide evidence of antipsoriatic efficacy by topical transdermal delivery of mIL-4. Therefore, topical transdermal gene transfer is attractive and offers future potential for application in human patients with other dermatogic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Cations / chemistry*
  • Cations / metabolism
  • Ear / blood supply
  • Ear / pathology
  • Female
  • Genetic Therapy*
  • Humans
  • Interleukin-4* / administration & dosage
  • Interleukin-4* / genetics
  • Interleukin-4* / therapeutic use
  • Liposomes* / administration & dosage
  • Liposomes* / chemical synthesis
  • Liposomes* / chemistry
  • Mice
  • Mice, Transgenic*
  • Particle Size
  • Psoriasis* / genetics
  • Psoriasis* / pathology
  • Psoriasis* / therapy
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Cations
  • Liposomes
  • Vascular Endothelial Growth Factor A
  • Interleukin-4