van der Maaden Koen, Trietsch Sebastiaan J, Kraan Heleen, Varypataki Eleni Maria, Romeijn Stefan, Zwier Raphäel, van der Linden Heiko J, Kersten Gideon, Hankemeier Thomas, Jiskoot Wim, Bouwstra Joke
Division of Drug Delivery Technology Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA, Leiden, the Netherlands.
Pharm Res. 2014 Jul;31(7):1846-54. doi: 10.1007/s11095-013-1288-9. Epub 2014 Jan 28.
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.
本研究的目的是开发一种廉价且快速的方法来生产中空微针以及一种用于将疫苗在预定深度注射到皮肤中的注射器，并测试该系统用于皮肤脊髓灰质炎疫苗接种的适用性。
通过氢氟酸蚀刻熔融石英毛细管来生产中空微针。开发了一种电磁注射器以控制插入速度（1 - 3米/秒）、深度（0 - 1000微米）和角度（10° - 90°）。对内径为20微米的中空微针在离体人皮肤上进行评估，随后通过在300微米深度以1米/秒的插入速度皮内微量注射9微升灭活脊髓灰质炎病毒疫苗（IPV）来免疫大鼠。检测大鼠血清中的IPV特异性IgG和病毒中和抗体。
由熔融石英毛细管制成的微针成功插入到选定深度，且针未堵塞或折断。皮内微量注射IPV诱导的免疫反应与传统肌肉注射免疫引发的反应相当。
我们成功开发了一种用于皮肤疫苗接种的中空微针技术，该技术能够对诸如插入深度和体积以及插入角度等影响免疫反应的因素进行基础研究。
