Microneedle-based transcutaneous immunisation in mice with N-trimethyl chitosan adjuvanted diphtheria toxoid formulations.
OBJECTIVE
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.
Bal
Suzanne M
SM
Division of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
Ding
Zhi
Z
Kersten
Gideon F A
GF
Jiskoot
Wim
W
Bouwstra
Joke A
JA
D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D000279:Administration, Cutaneous; D000818:Animals; D055598:Chemical Phenomena; D048271:Chitosan / Q000737:chemistry*; D002522:Chlorocebus aethiops; D004168:Diphtheria Toxoid / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D004867:Equipment Design; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007271:Injections, Intradermal; D051379:Mice; D008812:Mice, Hairless; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000008:administration & dosage; D009339:Needles; D012867:Skin / Q000378:metabolism; D014611:Vaccination / Q000295:instrumentation / Q000379:methods*; D014709:Vero Cells
D000277:Adjuvants, Pharmaceutic; D004168:Diphtheria Toxoid; D004337:Drug Carriers; D007074:Immunoglobulin G; C118071:N-trimethyl chitosan chloride; D048271:Chitosan