Novel hollow microneedle technology for depth-controlled microinjection-mediated dermal vaccination: a study with polio vaccine in rats.
OBJECTIVE
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.
Division of Drug Delivery Technology Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA, Leiden, the Netherlands.
Koen
K
van der Maaden
Sebastiaan J
SJ
Trietsch
Heleen
H
Kraan
Eleni Maria
EM
Varypataki
Stefan
S
Romeijn
Raphäel
R
Zwier
Heiko J
HJ
van der Linden
Gideon
G
Kersten
Thomas
T
Hankemeier
Wim
W
Jiskoot
Joke
J
Bouwstra
D000818:Animals; D004867:Equipment Design; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007271:Injections, Intradermal / Q000295:instrumentation; D008845:Microinjections / Q000295:instrumentation*; D009339:Needles; D011051:Poliomyelitis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D017955:Poliovirus / Q000276:immunology; D023321:Poliovirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D014611:Vaccination / Q000295:instrumentation*
D007074:Immunoglobulin G; D023321:Poliovirus Vaccines