Universiteit Leiden

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Dissertation

Towards controlled microneedle-mediated intradermal immunization

Traditionally, vaccines are administered intramuscularly using conventional hypodermic needles, which cause pain and distress. Microneedles are very short needles (smaller than 1 mm) that are practically invisible to the naked eye.

Author
Schipper, P.
Date
20 June 2019
Links
Thesis in Leiden Repository

Traditionally, vaccines are administered intramuscularly using conventional hypodermic needles, which cause pain and distress. Microneedles are very short needles (smaller than 1 mm) that are practically invisible to the naked eye. Microneedles may administer vaccine into the skin in a pain-free manner. By using the intradermal route for immunization, a high number of immune cells in the skin are targeted, which may result in more efficient immunization. In this thesis, several aspects of intradermal immunization were investigated by using hollow microneedles. As differently specialized immune cells reside at different depths in skin, immunization outcomes as function of injection depth in skin were investigated to determine effects of injection depth. Furthermore, as prolonged antigen exposure may enhance immune responses, immunization outcomes resulting from repeated fractional intradermal dosing schedules were compared to those resulting from bolus dosing schedules. Finally, a layer-by-layer coating approach was developed for solid microneedle arrays. In the layer-by-layer coating approach, alternating layers of antigen and polymer are coated onto the surface of microneedle arrays. This approach enabled coating and intradermal delivery of a precise amount of antigen. Intradermal immunization using layer-by-layer coated microneedle arrays resulted in effective immunization. In conclusion, these studies provide important insights towards controlled microneedle-mediated intradermal immunization.

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