Enhanced Mucosal Transport of Polysaccharide-Calcium Phosphate Nanocomposites for Oral Vaccination

Oral vaccine has attracted much interest, as it can stimulate both mucosal and systemic immunity with noninvasive and good patient compliance. However, the oral vaccine efficiency is strongly constrained by the low absorption of antigens in the small intestine due to the mucosal barriers. Physicochemical characteristics of nanoparticles (NPs) have strong effects on antigen mucosal penetration, helping to improve immune response. However, surface functions of NPs on mucosal transportation have not been clearly understood. In this work, we elaborately investigated how the surface characteristics of mucoadhesive chitosan and its derivant act on oral antigen absorption and immune response. Core-shell chitosan- and o-carboxymethyl chitosan-coated calcium phosphate (CaP) nanocomposites have been fabricated to investigate the surface property effect on protein antigen delivery using the oral route. The interaction between polymer-coated CaP NPs and the intestinal mucosal layer was studied using mucin absorption, NP diffusion through the mucus layer, NP permeability across the epithelium monolayer, and their cellular uptake by antigen presenting cells in detail. Ex vivo mucosa distribution and in vivo oral immunization of polymer-coated CaP nanocomposites were further examined to demonstrate that the surface property of NPs affects CaP diffusion and penetration through the mucosal layer. As expected, OVA orally delivered by polymer-coated CaP nanocomposites improved the response of mucosal immunity compared to antigen OVA itself in vivo.