Pharmaceutical Research

, Volume 25, Issue 2, pp 407–416

Gene Delivery to the Epidermal Cells of Human Skin Explants Using Microfabricated Microneedles and Hydrogel Formulations

Authors

  • Marc Pearton
    • Gene Delivery Research Group, Welsh School of PharmacyCardiff University
  • Chris Allender
    • Gene Delivery Research Group, Welsh School of PharmacyCardiff University
  • Keith Brain
    • Gene Delivery Research Group, Welsh School of PharmacyCardiff University
  • Alexander Anstey
    • Gwent Healthcare NHS TrustRoyal Gwent Hospital
  • Chris Gateley
    • Gwent Healthcare NHS TrustRoyal Gwent Hospital
  • Nicolle Wilke
    • Biomedical Microsystems TeamTyndall National Institute
  • Anthony Morrissey
    • Biomedical Microsystems TeamTyndall National Institute
    • Gene Delivery Research Group, Welsh School of PharmacyCardiff University
Research Paper

DOI: 10.1007/s11095-007-9360-y

Cite this article as:
Pearton, M., Allender, C., Brain, K. et al. Pharm Res (2008) 25: 407. doi:10.1007/s11095-007-9360-y

Abstract

Purpose

Microneedles disrupt the stratum corneum barrier layer of skin creating transient pathways for the enhanced permeation of therapeutics into viable skin regions without stimulating pain receptors or causing vascular damage. The cutaneous delivery of nucleic acids has a number of therapeutic applications; most notably genetic vaccination. Unfortunately non-viral gene expression in skin is generally inefficient and transient. This study investigated the potential for improved delivery of plasmid DNA (pDNA) in skin by combining the microneedle delivery system with sustained release pDNA hydrogel formulations.

Materials and Methods

Microneedles were fabricated by wet etching silicon in potassium hydroxide. Hydrogels based on Carbopol polymers and thermosensitive PLGA-PEG-PLGA triblock copolymers were prepared. Freshly excised human skin was used to characterise microneedle penetration (microscopy and skin water loss), gel residence in microchannels, pDNA diffusion and reporter gene (β-galactosidase) expression.

Results

Following microneedle treatment, channels of approximately 150–200 μm depth increased trans-epidermal water loss in skin. pDNA hydrogels were shown to harbour and gradually release pDNA. Following microneedle-assisted delivery of pDNA hydrogels to human skin expression of the pCMVβ reporter gene was demonstrated in the viable epidermis proximal to microchannels.

Conclusions

pDNA hydrogels can be successfully targeted to the viable epidermis to potentially provide sustained gene expression therein.

Key words

DNAhuman skinhydrogelmicroneedlesthermosensitive

Copyright information

© Springer Science+Business Media, LLC 2007