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Novel hollow microneedle technology for depth-controlled microinjection-mediated dermal vaccination: a study with polio vaccine in rats.

Pharmaceutical research (2014-01-29)
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 Bouwstra
ABSTRACT

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. 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. 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. 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.

MATERIALS
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