Improving stability and release kinetics of microencapsulated tetanus toxoid by co-encapsulation of additives
Improving stability and release kinetics of microencapsulated tetanus toxoid by co-encapsulation of additives
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DOI：
10.1023/a:1011998615267
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发表时间：
1998-07-01
影响因子：
3.7
通讯作者：
Gander, B
中科院分区：
文献类型：
--
作者：
Johansen, P;Men, Y;Gander, B
目的。用聚酯微球(MS)包裹破伤风环状病毒(Ttxd)进行单次注射免疫，迄今在动物体内表现出脉冲式体外释放和强烈的免疫应答，但没有增强作用。这被归因于长时间暴露在活体条件下的MS内环状稳定性不足。本研究考察了共胶囊化的假定稳定添加剂的效果。采用喷雾干燥法制备聚(D，L-乳酸-羟基乙酸共聚)(PLGA 50：50)和聚(D，L-乳酸)(PLGA)微球。结果GO-白蛋白、海藻糖和γ-羟丙基环糊精均能提高PLGA-50：50MS中的环状包封率，白蛋白可使抗原性Ttxd的包封率提高1~2个数量级。此外，对于白蛋白或白蛋白和海藻糖的混合物，Ttxd在1-2个月内以脉动模式释放。含有MS的优化Ttxd对于单剂疫苗递送系统可能是有价值的。
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.