目的研究破伤风类毒素聚乳酸微球中破伤风类毒素在制备过程和体内酸性环境中的稳定性及微球中附加剂的稳定作用。方法采用分子排阻色谱法，十二烷基硫酸钠聚丙烯酰胺凝胶电泳法，双向免疫扩散法。结果在制备过程和体内酸性环境中破伤风类毒素活性有轻微下降；附加剂增加微球包封率，改善药物释放，稳定蛋白质活性，尤其是具有多羟基结构的附加剂。结论破伤风类毒素聚乳酸微球中的蛋白质在制备过程和体内酸性环境中基本稳定，聚乳酸微球可望发展成为疫苗控释系统。

OBJECTIVE To investigate the stability of microencapsulated tetanus toxoid in the courses of preparation and release, and improve its stability by co encapsulation of additives. METHODS High pressure size exclusion chromatography, sodium dodecyl sulfatepolyacrylamide gel electrophoresis, double immunodiffusion were used.RESULTS The protein denaturation processes were ascribed to the course of preparation and release. Additives,especially the additives with polyhydroxy structures,enhancd the encapsulation efficiency in the microspheres,improved the release profiles and stabilized the active proteins,respectively. CONCLUSION The stability of tetanus toxoid loaded microspheres was satisfactory.The optimized tetanus toxoid containing microspheres may be valuable for a controlled vaccine delivery system.