Development of stabilized glucomannosylated chitosan nanoparticles using tandem crosslinking method for oral vaccine...

The aim of this study was to develop a novel platform technology, comprising of stable glucomannosylated chitosan nanoparticles, for oral immunization.

Chitosan nanoparticles were stabilized by tandem crosslinking using tripolyphosphate followed by glutaraldehyde. Process and formulation variables were optimized using a 'Box-Behnken' design. The in vitro and in vivo performances were established in RAW 264.7 and BALB/c mice, respectively.

The lyophilized formulation was exceptionally stable in simulated biological media and the enclosed antigen was conformationally stable. The mechanistic understanding of glucomannosylated chitosan nanoparticles in RAW 264.7 revealed transcellular uptake via both mannose and glucose transporter-mediated endocytosis. Glucomannan modification resulted in significantly higher systemic (serum IgG titer), mucosal (secretory IgA) and cell-mediated (IL-2 and IFN-γ) immune responses in comparison with nonmodified chitosan nanoparticles.

The present strategy is expected to contribute some novel tools for the oral delivery of numerous biomacromolecules.