title: Immunoadjuvant potential of cross-linked dextran microspheres mixed with chitosan nanospheres encapsulated with tetanus toxoid.
abstract: BACKGROUND
  Nasal mucosa is a desirable route for mucosal vaccine delivery. Mucosal co-administration of chitosan nanoparticles with absorption enhancers such as cross-linked dextran microspheres (CDM, Sephadex®) is a promising antigen delivery system.
  
  
  OBJECTIVE
  In the current study, the chitosan nanospheres loaded with tetanus toxoid (CHT:TT NPs) was prepared and characterized. The immune responses against tetanus toxoid after nasal administration of CHT:TT NPs alone or mixed with CDM were also determined.
  
  
  METHODS
  Chitosan nanospheres were prepared by ionic gelation method. Particle size, releasing profile and antigen stability were evaluated by dynamic light scattering, diffusion chamber and SDS-PAGE methods, respectively. Rabbits were nasally immunized with different formulations loaded with 40 Lf TT. After three times immunizations with 2 weeks intervals, sera IgG titres and nasal lavage sIgA titres were determined.
  
  
  RESULTS
  Mean size of CHT NPs and CHT:TT NPs were 205 ± 42 nm and 432 ± 85 nm, respectively. The release profile showed that 42.4 ± 10.5% of TT was released after 30 min and reached to a steady state after 1.5 h. Stability of encapsulated TT in nanospheres was confirmed by SDS-PAGE. The antibody titres showed that CHT:TT NPs-induced antibody titres were higher than TT solution. CHT NPs mixed with CDM induced the systemic IgG and nasal lavage sIgA titres higher than intranasal administration of TT solution (p < 0.001).
  
  
  CONCLUSIONS
  As the results indicated, these CHT:TT NPs when co-administered with CDM were able to induce more immune responses and have the potential to be used in mucosal immunization.
authors.affiliation: a Student Research Committee, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Haniyeh
authors.initials: H
authors.lastname: Pirouzmand
authors.affiliation: b Department of Pharmaceutical Control, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Bahman
authors.initials: B
authors.lastname: Khameneh
authors.affiliation: c Nanotechnology Research Center, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Tafaghodi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000281:Administration, Intranasal; D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003911:Dextrans / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D000067493:Dynamic Light Scattering; D004591:Electrophoresis, Polyacrylamide Gel; D018928:Immunity, Mucosal / Q000187:drug effects; D007115:Immunization Schedule; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D008863:Microspheres; D054118:Nanospheres; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010316:Particle Size; D011817:Rabbits; D012995:Solubility; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D003432:Cross-Linking Reagents; D003911:Dextrans; D004337:Drug Carriers; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D013745:Tetanus Toxoid; D048271:Chitosan
keywords: Nasal immunization; drug delivery; dry powder formulation; immune responses