Biodegradable microspheres as controlled-release tetanus toxoid delivery systems
| Autor: | Rajesh Gupta, Robert Langer, George R. Siber, María J. Alonso, Caroline Min |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Antigenicity
Polymers Drug Compounding Polyesters medicine.medical_treatment Capsules Mice Inbred Strains macromolecular substances complex mixtures Microbiology Mice chemistry.chemical_compound Polylactic Acid-Polyglycolic Acid Copolymer Tetanus Toxoid medicine Animals Lactic Acid Glycolic acid Chromatography General Veterinary General Immunology and Microbiology Tetanus technology industry and agriculture Public Health Environmental and Occupational Health Toxoid medicine.disease Controlled release Lactic acid PLGA Biodegradation Environmental Infectious Diseases chemistry Delayed-Action Preparations Lactates Microscopy Electron Scanning Molecular Medicine Female Adjuvant Polyglycolic Acid |
| Zdroj: | Vaccine. 12:299-306 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/0264-410x(94)90092-2 |
| Popis: | Purified tetanus toxoid, a high-molecular-weight protein, was entrapped within poly( L -lactic acid) (PLA) and poly( D , L -lactic/glycolic acid) (PLGA) microspheres prepared by either a solvent extraction or a solvent evaporation method carried out in a multiple emulsion system (water-in-oil-in-water). The physical integrity and antigenicity of the protein treated under different processing conditions were investigated. A reduction of antigenicity that was related to the percentage of aggregated protein was noticed under some experimental conditions. This partial loss of antigenicity was associated with the lyophilization process and affected by the nature of the organic solvent. All types of microspheres prepared with different molecular weight PLA and PLGA displayed a high protein-loading efficiency (>80%) but their size was strongly influenced by polymer molecular weight (3000 versus 100 000). Protein release pattern was influenced by both polymer molecular weight and composition (PLA versus PLGA). A constant release pattern after an induction period of 10 days was observed for microspheres composed of high-molecular-weight polymers (PLA and PLGA). The release rate was lower from PLA microspheres than from PLGA microspheres. In contrast, a continuously increasing release rate preceded by a burst was observed for low-molecular-weight (3000) PLGA microspheres. Microencapsulated tetanus toxoid was significantly more immunogenic in mice than fluid toxoid as determined by IgG anti-tetanus antibody levels and neutralizing antibodies. However, the magnitude and duration of the antibody response did not differ significantly from a similar dose of aluminium phosphate-adsorbed toxoid. We conclude that microencapsulated tetanus toxoid shows significant adjuvant activity. Further improvements in the formulation of microspheres which result in the release of higher concentrations of antigenically active tetanus toxoid for more prolonged periods may result in higher and more sustained antibody levels. |
| Databáze: | OpenAIRE |
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