Intradermal delivery of nanoparticulate vaccines using coated and hollow microneedles

Du, G. (2018)

Doctoral Thesis

In summary, the collective results described in this thesis show that nanoparticulate vaccines can be delivered intradermally by coated and hollow microneedles and evoke antigen-specific immune responses. The choice of both the nanoparticles and the microneedle(s) could have important influences on the immune responses. Microneedle arrays coated with antigen loaded and lipid bilayer fused mesoporous silica nanoparticles (MSNs) could be a promising system for convenient and fast intradermal delivery of protein antigen, although our results indicate that the system needs to be improved in order to obtain optimal immune responses. Moreover, antigen and adjuvant loaded nanoparticles can increase IgG2a (Th1) and CD8+ responses after intradermal delivery by hollow microneedles. This effect depends on the type and the physicochemical characteristics of the nanoparticles, in which smaller size and controlled release properties of antigen and adjuvant were found to correlate with the stronger effect. Finally, the combination of separate antigen loaded and adjuvant loaded nanoparticles may be as efficient as the antigen and adjuvant co-encapsulated nanoparticles for modification of the immune responses following intradermal immunization.

• Intradermal
• Nanoparticles
• Vaccine
• Coated
• Hollow
• Microneedle
• IgG2a
• T cell response

• All authors: Du, G.
• Supervisor: Bouwstra, J.A.; Jiskoot, W.
• Committee: Irth, H.; IJzerman, A.P.; Kuiper, J.; Frijlink, H.W.; Préat, V.; Mastrobattista, E.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drug Research (LADCR), Faculty of Science, Leiden University
• Date: 2018-10-30
• ISBN (print): 9789463750998
• Sponsorship: China Scholarship Council