title: Tetanus toxoids loaded glucomannosylated chitosan based nanohoming vaccine adjuvant with improved oral stability and immunostimulatory response.
abstract: OBJECTIVE
  The present report embarks on rational designing of stable and functionalized chitosan nanoparticles for oral mucosal immunization.
  
  
  METHODS
  Stable glucomannosylated sCh-GM-NPs were prepared by tandem cross linking method followed by lyophilization. The in vitro stability of antigen and formulation, cellular uptake and immunostimulatory response were assessed by suitable experimental protocol.
  
  
  RESULTS
  Stability testing ensured the chemical and conformation permanency of encapsulated TT as well as robustness of sCh-GM-NPs in simulated biological media. The antigen release from sCh-GM-NPs followed initial burst followed by controlled Weibull's type of release profile. The higher intracellular uptake of sCh-GM-NPs in Raw 264.7 and Caco-2 was concentration and time dependent which mainly attributed to Clathrin and receptor mediated endocytosis via mannose and glucose receptor. The in vivo evaluation in animals revealed that sCh-GM-NPs posed significantly (p < 0.001) higher humoral, mucosal and cellular immune response than other counterparts. More importantly, commercial TT vaccine administered through oral or intramuscular route was unable to elicit all type of immune response.
  
  
  CONCLUSIONS
  The sCh-GM-NPs could be considered as promising vaccine adjuvant for oral tetanus immunization. Additionally, this technology expected to benefit the design and development of stable peroral formulation for administration of protein, peptides and variety of other antigens.
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, 160 062, 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: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008264:Macrophages / Q000276:immunology; D008297:Male; D008351:Mannans / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000276:immunology*; D053758:Nanoparticles / Q000737:chemistry*; D013499:Surface Properties; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008351:Mannans; D013745:Tetanus Toxoid; C022901:(1-6)-alpha-glucomannan; D048271:Chitosan