Development of chitosan–pullulan composite nanoparticles for nasal delivery of vaccines: optimisation and cellular studies

Abstract

Nasal immunisation with nanoparticles has already shown promising results. In this study, nanoparticle composites carrying BSA for nasal vaccination prepared using electrostatic interaction process between polycation N-trimethyl chitosan chloride (TMC), chitosan glutamate (CG), chitosan chloride (CCl) and polyanion carboxymethyl pullulan (CMP). A mass ratio of 2:1 for TMC-CMP combination produced stable nanocarriers. For CCl-CMP and CG-CMP formulations needed a mass ratio of 3:1. Loading efficiency was >90% for all formulations. Nanoparticles’ size ranged from 207 to 603 nm. The surface charge of the complexes varied between +14 and +33 mV. SDS-PAGE integrity of the model antigen was also demonstrated. MTT studies showed that nanoparticle composites were less toxic to Calu-3 cells than the particles of cationic polymers alone. FITC-BSA loaded nanoparticles efficiently taken up by J774A.1 macrophages as confirmed by confocal microscopy highlighting the potential of these novel nanoparticulate carriers’ use for nasal vaccination.

• Carboxymethyl pullulan
• cellular uptake
• chitosan derivatives
• nanoparticles
• nasal vaccination
• N-trimethyl chitosan chloride
• 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.