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Pharmaceutical Research

, Volume 31, Issue 7, pp 1846–1854 | Cite as

Novel Hollow Microneedle Technology for Depth-Controlled Microinjection-Mediated Dermal Vaccination: A Study with Polio Vaccine in Rats

  • Koen van der Maaden
  • Sebastiaan J. Trietsch
  • Heleen Kraan
  • Eleni Maria Varypataki
  • Stefan Romeijn
  • Raphäel Zwier
  • Heiko J. van der Linden
  • Gideon Kersten
  • Thomas Hankemeier
  • Wim Jiskoot
  • Joke BouwstraEmail author
Research Paper

ABSTRACT

Purpose

The aim of the study was to develop a cheap and fast method to produce hollow microneedles and an applicator for injecting vaccines into the skin at a pre-defined depth and test the applicability of the system for dermal polio vaccination.

Methods

Hollow microneedles were produced by hydrofluoric acid etching of fused silica capillaries. An electromagnetic applicator was developed to control the insertion speed (1–3 m/s), depth (0–1,000 μm), and angle (10°–90°). Hollow microneedles with an inner diameter of 20 μm were evaluated in ex vivo human skin and subsequently used to immunize rats with inactivated poliovirus vaccine (IPV) by an intradermal microinjection of 9 μL at a depth of 300 μm and an insertion speed of 1 m/s. Rat sera were tested for IPV-specific IgG and virus-neutralizing antibodies.

Results

Microneedles produced from fused silica capillaries were successfully inserted into the skin to a chosen depth, without clogging or breakage of the needles. Intradermal microinjection of IPV induced immune responses comparable to those elicited by conventional intramuscular immunization.

Conclusions

We successfully developed a hollow microneedle technology for dermal vaccination that enables fundamental research on factors, such as insertion depth and volume, and insertion angle, on the immune response.

KEY WORDS

intradermal immunization microinjections microneedles polio vaccine vaccine delivery 

ABBREVIATIONS

IPV

Inactivated polio vaccine

OPV

Oral polio vaccine

VN

Virus neutralizing

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

Koen van der Maaden and Sebastiaan J. Trietsch contributed equally. We thank the Electronics Department at Leiden University for their help in the development of the microneedle applicator. Furthermore, we thank Aat Mulder for preparing the cryosections of rat skin and Pim Schipper for performing the microinjections into ex vivo human skin and the subsequent cryosections. This work was (co)financed by the Netherlands Metabolomics Centre (NMC), which is a part of The Netherlands Genomics Initiative/Netherlands Organization for Scientific Research.

Supplementary material

11095_2013_1288_MOESM1_ESM.docx (44 kb)
Figure S1 (DOCX 44 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Koen van der Maaden
    • 1
  • Sebastiaan J. Trietsch
    • 2
  • Heleen Kraan
    • 3
  • Eleni Maria Varypataki
    • 1
  • Stefan Romeijn
    • 1
  • Raphäel Zwier
    • 4
  • Heiko J. van der Linden
    • 2
  • Gideon Kersten
    • 1
    • 3
  • Thomas Hankemeier
    • 2
  • Wim Jiskoot
    • 1
  • Joke Bouwstra
    • 1
    Email author
  1. 1.Division of Drug Delivery Technology Leiden Academic Centre for Drug Research (LACDR)Leiden UniversityLeidenthe Netherlands
  2. 2.Division of Analytical Biosciences Leiden Academic Centre for Drug Research (LACDR)Leiden UniversityLeidenthe Netherlands
  3. 3.Institute for Translational Vaccinology (Intravacc)Bilthoventhe Netherlands
  4. 4.Fine Mechanical Department, Leiden Institute of Physics (LION)Leiden UniversityLeidenthe Netherlands

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