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  • 1
    ISSN: 1573-904X
    Keywords: antigen delivery ; PLGA microspheres ; tetanus toxoid ; antigenic stability ; stabilizing additives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Tetanus toxoid (Ttxd) encapsulated in polyester microspheres (MS) for single injection immunization have so far given pulsatile in vitro release and strong immune response in animals, but no boosting effect. This has been ascribed to insufficient toxoid stability within the MS exposed to in vivo conditions over a prolonged time period. This study examined the effect of co-encapsulated putative stabilizing additives. Methods. Two different Ttxd were encapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA 50:50) and poly(D,L-lactic acid) (PLA) MS by spray-drying. The influence of co-encapsulated additives on toxoid stability, loading in and release from the MS, was studied by fluorimetry and ELISA. Results. Co-encapsulated albumin, trehalose and γ-hydroxypropyl cyclodextrin all improved the toxoid encapsulation efficiency in PLGA 50:50 MS. Albumin increased the encapsulation efficiency of antigenic Ttxd by one to two orders of magnitude. Further, with albumin or a mixture of albumin and trehalose ELISA responsive Ttxd was released over 1−2 months following a pulsatile pattern. Conclusions. Optimized Ttxd containing MS may be valuable for a single-dose vaccine delivery system.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: biodegradable microspheres ; poly(D,L-lactide-co-glycolide) ; tetanus toxoid ; vaccine ; antibody response ; stabilizing agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Antigenic proteins encapsulated in biodegradable polyester microspheres (MS) can slowly denature or aggregate, which results in decreased antigenicity. In this study, we have evaluated the ability of co-encapsulated additives to protect against the loss of tetanus toxoid (TT) antigenicity. Methods. Antibody responses were analyzed after immunization of mice with TT microencapsulated in the presence of additives (TT-MS-additive). Results. Immunization with TT-MS-additives gave rise to higher responses than those obtained in the absence of additive. BSA, trehalose, -γ-hydroxypropylcyclodextrin and calcium salts preserved the immunogenicity of the incorporated antigen with the highest efficacy. Sustained responses were obtained with mixtures of fast and slowly releasing TT-MS containing BSA plus trehalose or calcium salts. Conclusions. The selected additives may stabilize the antigen in MS during storage and rehydration in body fluids. Regulated antigen release from MS-based vaccines permits a reduction of the antigen dose and optimization of single-dose vaccine formulations.
    Type of Medium: Electronic Resource
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