Improved immunogenicity of a core-coated tetanus toroid delivery system

A new microparticulate delivery system composed of a stabilizing gelatin/po loxamer microcore surrounded by a PLGA coat was designed to improve the sta bility of tetanus toroid (TT) encapsulated in PLGA microspheres. Microcores were prepared by a spray-congealing technique and encapsulated within PLGA using an oil-in-oil (o/o) solvent evaporation technique. SEM analysis of t he cross-sections of the microcapsules revealed the adequate encapsulation of the cores, showing an intimate contact between the core and the coating. This structure was responsible for an osmotic phenomenon observed in vitro , which led to the release of the encapsulated TT in a short period of time . Nevertheless, it was observed that the release was affected by the presen ce of the poloxamer in the core: microspheres without poloxamer in the core exhibit a faster release (2 h) than those that incorporate the surfactant (24 h). The in vivo evaluation of this system showed that the encapsulated toroid induced a low but continuous levels of neutralizing antibodies (Nt), whereas those obtained for the control (aluminum phosphate-adsorbed toroid ) decreased after reaching the maximum level at 14 weeks. Moreover, the adm inistration of a mixture of encapsulated and adsorbed TT led to significant higher and more prolonged Nt levels than those measured for the adsorbed t oroid. (C) 1999 Elsevier Science Ltd. All rights reserved.