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

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.

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Abbreviations

IPV:

Inactivated polio vaccine

OPV:

Oral polio vaccine

VN:

Virus neutralizing

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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.

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Correspondence to Joke Bouwstra.

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van der Maaden, K., Trietsch, S.J., Kraan, H. et al. Novel Hollow Microneedle Technology for Depth-Controlled Microinjection-Mediated Dermal Vaccination: A Study with Polio Vaccine in Rats. Pharm Res 31, 1846–1854 (2014). https://doi.org/10.1007/s11095-013-1288-9

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KEY WORDS

  • intradermal immunization
  • microinjections
  • microneedles
  • polio vaccine
  • vaccine delivery