Microneedle-based transcutaneous immunisation in mice with N-trimethyl chitosan adjuvanted diphtheria toxoid formulations

Pharm Res. 2010 Sep;27(9):1837-47. doi: 10.1007/s11095-010-0182-y. Epub 2010 Jun 18.

Abstract

Purpose: The purpose of this study was to gain insight into the delivery and immunogenicity of N-trimethyl chitosan (TMC) adjuvanted diphtheria toxoid (DT) formulations applied transcutaneously with microneedles.

Methods: Mice were vaccinated with DT-loaded TMC nanoparticles, a solution of TMC and DT (TMC/DT) or DT alone. The formulations were applied onto the skin before or after microneedle treatment with two different 300-microm-long microneedle arrays and also injected intradermally (ID). As a positive control, alum-adjuvanted DT (DT-alum) was injected subcutaneously (SC). Ex vivo confocal microscopy studies were performed with rhodamine-labelled TMC.

Results: Independent of the microneedle array used and the sequence of microneedle treatment and vaccine application, transcutaneous immunisation with the TMC/DT mixture elicited 8-fold higher IgG titres compared to the TMC nanoparticles or DT solution. The toxin-neutralising antibody titres from this group were similar to those elicited by SC DT-alum. After ID immunisation, both TMC-containing formulations induced enhanced titres compared to a DT solution. Confocal microscopy studies revealed that transport of the TMC nanoparticles across the microneedle conduits was limited compared to a TMC solution.

Conclusions: In conclusion, TMC has an adjuvant function in transcutaneous immunisation with microneedles, but only if applied in a solution.

MeSH terms

  • Adjuvants, Pharmaceutic / chemistry*
  • Administration, Cutaneous
  • Animals
  • Chemical Phenomena
  • Chitosan / chemistry*
  • Chlorocebus aethiops
  • Diphtheria Toxoid / administration & dosage*
  • Diphtheria Toxoid / chemistry
  • Diphtheria Toxoid / immunology
  • Diphtheria Toxoid / pharmacokinetics
  • Drug Carriers / chemistry*
  • Equipment Design
  • Female
  • Immunoglobulin G / blood
  • Injections, Intradermal
  • Mice
  • Mice, Hairless
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Nanoparticles / administration & dosage
  • Needles*
  • Skin / metabolism
  • Vaccination / instrumentation
  • Vaccination / methods*
  • Vero Cells

Substances

  • Adjuvants, Pharmaceutic
  • Diphtheria Toxoid
  • Drug Carriers
  • Immunoglobulin G
  • N-trimethyl chitosan chloride
  • Chitosan