title: Development of stabilized glucomannosylated chitosan nanoparticles using tandem crosslinking method for oral vaccine delivery.
abstract: OBJECTIVE
  The aim of this study was to develop a novel platform technology, comprising of stable glucomannosylated chitosan nanoparticles, for oral immunization.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The present strategy is expected to contribute some novel tools for the oral delivery of numerous biomacromolecules.
authors.affiliation: Center for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research, SAS Nagar, Punjab, 160062, India.
authors.forename: Harshad
authors.initials: H
authors.lastname: Harde
authors.forename: Ashish Kumar
authors.initials: AK
authors.lastname: Agrawal
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
mesh_terms: D000284:Administration, Oral; D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D016503:Drug Delivery Systems; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008351:Mannans / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D014612:Vaccines / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D007376:Interleukin-2; D008351:Mannans; D014612:Vaccines; C022901:(1-6)-alpha-glucomannan; D048271:Chitosan
keywords: APC; chitosan; glucomannan; nanoparticle; oral immunization