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The handle http://hdl.handle.net/1887/66514 holds various files of this Leiden University dissertation.

Author: Du, G.

Title: Intradermal delivery of nanoparticulate vaccines using coated and hollow microneedles

Issue Date: 2018-10-30

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Intraderm a l d e livery of nanoparticulate

vaccines using coated and hollow

microneedles

Guangsheng Du

杜广盛

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Intradermal delivery of nanoparticulate vaccines using coated and hollow microneedles

PhD thesis with summary in Dutch

©2018 Guangsheng Du. All rights reserved. No part of this thesis may be reproduced or transmitted in any form or by any means without written permission of the author.

Cover: Schematic diagram of the microneedle-mediated delivery of nanoparticulate vaccines and the subsequent uptake of the vaccines by antigen- presenting cells

Cover design: Guangsheng Du

Printing: Ridderprint BV, Ridderkerk, The Netherlands ISBN: 978-94-6375-099-8

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Intradermal delivery of nanoparticulate

vaccines using coated and hollow

microneedles

PROEFSCHRIFT

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden,

op gezag van de Rector Magnificus prof.mr. C.J.J.M. Stolker, volgens besluit van het College voor Promoties

te verdedigen op dinsdag 30 Oktober 2018 klokke 15.00 uur

door

Guangsheng Du

Geboren te Linyi, China in 1988

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Promotoren:

Prof. Dr. J.A. Bouwstra Prof. Dr. W. Jiskoot

Promotiecommissie:

Prof. Dr. H. Irth, LACDR, Chair

Prof. Dr. A.P. Ijzerman, LACDR, Secretary Prof. Dr. J. Kuiper, LACDR

Prof. Dr. H.W. Frijlink, Universiteit Groningen Prof. Dr. V. Préat, Universite catholique de Louvain Dr. E. Mastrobattista, Universiteit Utrecht

The studies presented in this thesis were performed at the Division of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.The studies were partially financed by the Chinese Scholarship Council (CSC). The publication of this thesis was financially supported by the Leiden University.

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Table of Contents

Chapter 1 General introduction, aim and outline of this thesis ... 1

Chapter 2 Mesoporous silica nanoparticle-coated microneedle arrays for intradermal antigen delivery ... 13

Chapter 3 Hollow microneedle-mediated intradermal delivery of model vaccine antigen- loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium ... 37

Chapter 4 Intradermal vaccination with hollow microneedles: a comparative study of various protein antigen and adjuvant encapsulated nanoparticles ... 59

Chapter 5 Immunogenicity of diphtheria toxoid and poly(I:C) loaded cationic liposomes after hollow microneedle-mediated intradermal injection in mice ... 81

Chapter 6 Coated and hollow microneedle-mediated intradermal immunization in mice with diphtheria toxoid loaded mesoporous silica nanoparticles ... 97

Chapter 7 Summarizing discussion and prospects ... 117

Appendices

Nederlandse samenvatting... 127 Curriculum Vitae ... 133 List of publications ... 135

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