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Improving Stability and Release Kinetics of Microencapsulated Tetanus Toxoid by Co-Encapsulation of Additives

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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.

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Authors and Affiliations

  1. Department of Pharmacy, ETH-Zürich, Winterthurerstr. 190, CH-8057, Zürich

    Pål Johansen, Hans P. Merkle & Bruno Gander

  2. Institute of Biochemistry, University of Lausanne, Chemin des Boveresses 155, CH-1066, Epalinges

    Ying Men, Régine Audran & Giampietro Corradin

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  1. Pål Johansen
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  2. Ying Men
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  5. Hans P. Merkle
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  6. Bruno Gander
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Johansen, P., Men, Y., Audran, R. et al. Improving Stability and Release Kinetics of Microencapsulated Tetanus Toxoid by Co-Encapsulation of Additives. Pharm Res 15, 1103–1110 (1998). https://doi.org/10.1023/A:1011998615267

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