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

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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.

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Acknowledgements

The authors acknowledge the BBSRC for financial support of MP.

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Authors and Affiliations

  1. Gene Delivery Research Group, Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3XF, UK

    Marc Pearton, Chris Allender, Keith Brain & James Birchall

  2. Gwent Healthcare NHS Trust, Royal Gwent Hospital, Cardiff Road, Newport, South Wales, NP20 2UB, UK

    Alexander Anstey & Chris Gateley

  3. Biomedical Microsystems Team, Tyndall National Institute, Prospect Row, Cork, Ireland

    Nicolle Wilke & Anthony Morrissey

Authors
  1. Marc Pearton
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  2. Chris Allender
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  3. Keith Brain
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  6. Nicolle Wilke
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  7. Anthony Morrissey
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  8. James Birchall
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Correspondence to James Birchall.

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Pearton, M., Allender, C., Brain, K. et al. Gene Delivery to the Epidermal Cells of Human Skin Explants Using Microfabricated Microneedles and Hydrogel Formulations. Pharm Res 25, 407–416 (2008). https://doi.org/10.1007/s11095-007-9360-y

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  • DOI: https://doi.org/10.1007/s11095-007-9360-y

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