Coated and Hollow Microneedle-Mediated Intradermal Immunization in Mice with Diphtheria Toxoid Loaded Mesoporous Silica Nanoparticles

Guangsheng Du, Laura Woythe, Koen van der Maaden, Mara Leone, Stefan Romeijn, Alexander Kros, Gideon Kersten, Wim Jiskoot, Joke A. Bouwstra (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)

Abstract

Purpose: To examine the immunogenicity of diphtheria toxoid (DT) loaded mesoporous silica nanoparticles (MSNs) after coated and hollow microneedle-mediated intradermal immunization in mice. Methods: DT was loaded into MSNs and the nanoparticle surface was coated with a lipid bilayer (LB-MSN-DT). To prepare coated microneedles, alternating layers of negatively charged LB-MSN-DT and positively charged N-trimethyl chitosan (TMC) were coated onto pH-sensitive microneedle arrays via a layer-by-layer approach. Microneedle arrays coated with 5 or 3 layers of LB-MSN-DT were used to immunize mice and the elicited antibody responses were compared with those induced by hollow microneedle-injected liquid formulation of LB-MSN-DT. Liquid DT formulation with and without TMC (DT/TMC) injected by a hollow microneedle were used as controls. Results: LB-MSN-DT had an average size of about 670 nm and a zeta potential of −35 mV. The encapsulation efficiency of DT in the nanoparticles was 77%. The amount of nano-encapsulated DT coated onto the microneedle array increased linearly with increasing number of the coating layers. Nano-encapsulated DT induced stronger immune responses than DT solution when delivered intradermally via hollow microneedles, but not when delivered via coated microneedles. Conclusion: Both the nano-encapsulation of DT and the type of microneedles affect the immunogenicity of the antigen.

Original languageEnglish
Article number189
JournalPharmaceutical Research
Volume35
Issue number10
DOIs
Publication statusPublished - 1 Oct 2018
Externally publishedYes

Keywords

  • coated microneedles
  • diphtheria toxoid
  • hollow microneedles
  • intradermal vaccination
  • mesoporous silica nanoparticles
  • Immunogenicity, Vaccine
  • Silicon Dioxide/chemistry
  • Immunization
  • Humans
  • Diphtheria Toxoid/administration & dosage
  • Drug Delivery Systems
  • Particle Size
  • Animals
  • Surface Properties
  • Nanoparticles/chemistry
  • Drug Compounding
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Porosity
  • Injections, Intradermal

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