title: Development and evaluation of chitosan microspheres for tetanus, diphtheria and divalent vaccines: a comparative study of subcutaneous and intranasal administration in mice.
abstract: BACKGROUND
  There is a need to use the new technologies to induce immunity with minimum number of vaccination sessions to ensure compliance with reducing cost.
  
  
  OBJECTIVE
  To develop single shot vaccines of tetanus, diphtheria and divalent toxoids microsphere's formulations and to induce their immune response after intranasal and subcutaneous administration in mice.
  
  
  METHODS
  The microspheres were prepared using different concentrations of chitosan. Microsphere's morphology, particle size analysis, encapsulation efficiency and antigen integrity were performed and the best formulations were selected for in vitro and in vivo testing in mice.
  
  
  RESULTS
  The developed microspheres have a yield percent of 70.3-91.5%. In vitro release of antigens indicated that tetanus release was increased up to 75 and 81% post T5 and TD5 formulations respectively, whereas diphtheria cumulative release increased up to 74 and 69% post D3 and TD5, respectively.
  
  
  CONCLUSIONS
  Antibody levels produced were lower than that obtained from alum adsorbed vaccine but higher than the minimum level required to induce immunogenicity (>0.01 IU/mL). The subcutaneous route of administration was superior over the intranasal route in producing higher antibody levels.
  
  
  CONCLUSIONS
  Chitosan microspheres were developed successfully and prove that chitosan represents a good candidate for vaccines delivery.
authors: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
authors: Fahima M
authors: FM
authors: Hashem
authors: Sahar A
authors: SA
authors: Fahmy
authors: Aly M
authors: AM
authors: El-Sayed
authors: Majid M
authors: MM
authors: Al-Sawahli
mesh_terms: D000279:Administration, Cutaneous; D000281:Administration, Intranasal / Q000379:methods; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D004165:Diphtheria / Q000276:immunology*; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D022422:Diphtheria-Tetanus Vaccine / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods; D008297:Male; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D013742:Tetanus / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology
chemical_list: D000906:Antibodies; D000941:Antigens; D004168:Diphtheria Toxoid; D022422:Diphtheria-Tetanus Vaccine; D013745:Tetanus Toxoid; D048271:Chitosan