Targeted, needle-free vaccinations in skin using multilayered, densely-packed dissolving microprojection arrays

Anthony P. Raphael, Tarl W. Prow, Michael L. Crichton, Xianfeng Chen, Germain J P Fernando, Mark A F Kendall

Research output: Contribution to journalArticlepeer-review

137 Citations (Scopus)

Abstract

Targeting of vaccines to abundant immune cell populations within our outer thin skin layers using miniaturized devices-much thinner than a needle and syringe, could improve the efficacy of vaccines (and other immunotherapies). To meet this goal, a densely packed dissolving microprojection array (dissolving Nanopatch) is designed, achieving functional miniaturization by 1) formulating small microneedles (two orders of magnitude smaller than a standard needle and syringe) and 2) multiple layering of the payload within microprojections with tight tolerances (of the order of a micrometer). The formulation method is suitable to many vaccines because it is without harsh or complex chemical processes, and it is performed at low temperatures and at a neutral pH. When the formulated dNPs are applied to skin, consistent and robust penetration is achieved, rapidly targeting the skin strata of interest (<5 min; significantly faster than larger dissolving microneedles that have been previously reported). Resultant diffusion is significantly enhanced within the dermis compared with the epidermis. Using two different antigens (ovalbumin and a commercial trivalent influenza vaccine [Fluvax2008]), the administration of these dissolving patches generate robust systemic immune responses in a mouse model. To the authors' knowledge, this is the first report of successful vaccination with any form of dissolving microneedles. The patches made by this method therefore have the potential for pain-free, needle-free, and effective vaccination in humans.

Original languageEnglish
Pages (from-to)1785-1793
Number of pages9
JournalSmall
Volume6
Issue number16
DOIs
Publication statusPublished - 12 Aug 2010

Keywords

  • Drug delivery
  • Microneedles
  • Microstructures
  • Skin
  • Vaccines

ASJC Scopus subject areas

  • Biomaterials
  • Engineering (miscellaneous)
  • Biotechnology
  • General Medicine

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