Immunostimulatory effect of tetanus toxoid loaded chitosan nanoparticles following microneedles assisted immunization

The present study investigated potential of tetanus toxoid loaded chitosan nanoparticles (TT-Ch-NPs) following bare topical and microneedles assisted immunization. The TT-Ch-NPs were prepared by ionotropic gelation method using poly(sodium-4-styrene sulfonate) (PSS) as crosslinking agent which exhibited ~208 nm size and ~99% entrapment efficiency. The manufacturing process did not have any detrimental effect on integrity and conformation of antigen. The in vitro analysis demonstrated higher skin penetration following microneedles assisted immunization. In vivo immunization studies exhibited that TT-Ch-NPs delivered through microneedles induced comparable IgG and IgG1 titer, yet higher IgG2a titer than commercial TT vaccine. Similarly, microneedles assisted administration of TT-Ch-NPs generated higher Th1 cytokines, albeit no significant alteration in Th2 cytokines levels than commercial TT vaccine. In conclusion, microneedles assisted administration of TT-Ch-NPs especially via hollow microneedles (HMN) could be considered as best preferred route for immunization due to induction of more balanced Th1/Th2 biased immune response. From the Clinical Editor: The use of skin as a route for vaccination has been a clinically important topic for some time. In this article, the authors investigated the efficacy of both solid microneedles and hollow microneedles as methods for topical delivery of tetanus toixoid. The positive finding in the experiments could provide a better method for vaccination in the clinical setting in the future.