Eudragit® L100-coated mannosylated chitosan nanoparticles for oral protein vaccine delivery

The aim of this study was to develop a novel biodegradable polymeric carrier for the delivery of protein vaccine orally in order to target the antigen presenting cells (APCs) in the region of Peyer's patches (PPs). Here, bovine serum albumin (BSA) was chosen as a model protein vaccine and was loaded into the mannosylated chitosan nanoparticles (MCS NPs) by ionic gelation method with tripolyphosphate (TPP), followed by coating MCS NPs with Eudragit® L100 (Eud) by electrostatic interaction. The spherical NPs were successfully prepared with appropriate particle size around 558.2 ± 35.6 nm, high entrapment efficiency about 90.38 ± 9.12%, good stability and reasonable release behavior in the simulated gastrointestinal fluid, meanwhile high resistance of enzymatic and acid degradations were verified. The targeting ability of the NPs to PPs in rat was investigated by a closed ileal loop assay, where fluorescence visualization was performed. MCS NPs were accumulated more specifically into PPs after Eudragit® L100 dissolved in intestinal juices. Oral immunization using BSA-loaded Eudragit® L100-coated MCS NPs was found to elicit strong systemic IgG antibody and mucosal IgA responses. These results suggested that enteric-coated MCS NPs could serve as a promising carrier for oral protein vaccine delivery.