Improving stability and release kinetics of microencapsulated tetanus toxoid by co-encapsulation of additives

Purpose. Tetanus toroid (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 toroid 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 toroid stability, loading in and release from the MS, was studied by fluorimetry and ELISA. Results, Go-encapsulated albumin, trehalose and gamma-hydrorypropyl cyclodextrin all improved the toroid 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.