Development and evaluation of chitosan microspheres for tetanus, diphtheria and divalent vaccines: a comparative study of subcutaneous and intranasal administration in mice

Pharm Dev Technol. 2013 Sep-Oct;18(5):1175-85. doi: 10.3109/10837450.2011.618949. Epub 2011 Oct 10.

Abstract

Context: There is a need to use the new technologies to induce immunity with minimum number of vaccination sessions to ensure compliance with reducing cost.

Objectives: 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.

Materials and 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.

Discussion: 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.

Conclusion: Chitosan microspheres were developed successfully and prove that chitosan represents a good candidate for vaccines delivery.

MeSH terms

  • Administration, Cutaneous
  • Administration, Intranasal / methods
  • Animals
  • Antibodies / immunology
  • Antigens / administration & dosage
  • Antigens / chemistry
  • Antigens / immunology
  • Chemistry, Pharmaceutical / methods
  • Chitosan / administration & dosage
  • Chitosan / chemistry*
  • Chitosan / immunology
  • Diphtheria / immunology*
  • Diphtheria Toxoid / administration & dosage
  • Diphtheria Toxoid / chemistry*
  • Diphtheria Toxoid / immunology
  • Diphtheria-Tetanus Vaccine / administration & dosage
  • Diphtheria-Tetanus Vaccine / chemistry*
  • Diphtheria-Tetanus Vaccine / immunology
  • Drug Delivery Systems / methods
  • Male
  • Mice
  • Microspheres
  • Particle Size
  • Tetanus / immunology*
  • Tetanus Toxoid / administration & dosage
  • Tetanus Toxoid / chemistry*
  • Tetanus Toxoid / immunology

Substances

  • Antibodies
  • Antigens
  • Diphtheria Toxoid
  • Diphtheria-Tetanus Vaccine
  • Tetanus Toxoid
  • Chitosan