Development of chitosan–pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies

Abstract

Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239–405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC–pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th₁/Th₂ response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

• Carboxymethyl pullulan
• chitosan derivatives
• intramuscular immunisation
• nanoparticles
• nasal immunisation
• polyion complexation

Acknowledgements

We would like to thank to Mr. Dave McCarthy, The UCL School of Pharmacy, University of London, for producing Transmission Electron Microscopy images.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.