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Related Experiment Videos

Biodegradable microspheres as controlled-release tetanus toxoid delivery systems

M J Alonso1, R K Gupta, C Min

  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139.

Vaccine
|March 1, 1994
PubMed
Summary

Microencapsulating tetanus toxoid in poly(lactic acid) or poly(lactic-co-glycolic acid) microspheres enhances immunogenicity. This novel delivery system shows significant adjuvant activity, improving antibody responses in mice.

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Area of Science:

  • Biomaterials Science
  • Vaccine Technology
  • Drug Delivery Systems

Background:

  • Tetanus toxoid is a key component in vaccines.
  • Developing effective delivery systems for protein-based antigens is crucial for enhancing immunogenicity.
  • Biodegradable polymers like poly(L-lactic acid) (PLA) and poly(D,L-lactic/glycolic acid) (PLGA) are widely studied for drug encapsulation.

Purpose of the Study:

  • To investigate the encapsulation of tetanus toxoid in PLA and PLGA microspheres.
  • To evaluate the impact of processing conditions on protein integrity and antigenicity.
  • To assess the immunogenicity and release profile of microencapsulated tetanus toxoid.

Main Methods:

  • Tetanus toxoid was encapsulated in PLA and PLGA microspheres using solvent extraction and evaporation methods within a multiple emulsion system.

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  • Physical integrity and antigenicity were assessed under various processing conditions, including lyophilization and different organic solvents.
  • Protein loading efficiency, microsphere size, and in vitro release patterns were analyzed.
  • In vivo immunogenicity was evaluated in mice by measuring IgG anti-tetanus antibody levels and neutralizing antibodies.

    • Main Results:

    • High protein-loading efficiency (>80%) was achieved for all microspheres.
    • Microsphere size was significantly influenced by polymer molecular weight.
    • A reduction in antigenicity was observed under specific conditions, linked to lyophilization and organic solvent choice.
    • PLA and PLGA microspheres showed distinct protein release patterns influenced by polymer characteristics.
    • Microencapsulated tetanus toxoid demonstrated significantly higher immunogenicity in mice compared to fluid toxoid.

    Conclusions:

    • Microencapsulation of tetanus toxoid in PLA and PLGA microspheres is feasible with high loading efficiency.
    • Processing conditions, particularly lyophilization and solvent type, can affect protein antigenicity.
    • The microsphere system exhibits significant adjuvant activity, enhancing the immune response.
    • This microencapsulation approach offers a promising strategy for improved vaccine delivery.