Johansen P, Men Y, Audran R, Corradin G, Merkle H P, Gander B
Department of Pharmacy, ETH-Zürich.
Pharm Res. 1998 Jul;15(7):1103-10. doi: 10.1023/a:1011998615267.
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.
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.
Co-encapsulated albumin, trehalose and gamma-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.
Optimized Ttxd containing MS may be valuable for a single-dose vaccine delivery system.
迄今为止，包裹在聚酯微球（MS）中用于单次注射免疫的破伤风类毒素（Ttxd）在体外呈现脉冲式释放，在动物体内引发强烈免疫反应，但无增强效果。这归因于在长时间暴露于体内条件下，微球内类毒素稳定性不足。本研究考察了共包裹假定的稳定添加剂的效果。
通过喷雾干燥将两种不同的Ttxd包裹于聚（D，L-乳酸-共-乙醇酸）（PLGA 50:50）和聚（D，L-乳酸）（PLA）微球中。通过荧光测定法和酶联免疫吸附测定法研究共包裹添加剂对类毒素稳定性、在微球中的负载及从微球中释放的影响。
共包裹的白蛋白、海藻糖和γ-羟丙基环糊精均提高了Ttxd在PLGA 50:50微球中的包裹效率。白蛋白使抗原性Ttxd的包裹效率提高了一到两个数量级。此外，使用白蛋白或白蛋白与海藻糖的混合物时，ELISA反应性Ttxd在1 - 2个月内呈脉冲模式释放。
优化后的含Ttxd微球对于单剂量疫苗递送系统可能具有重要价值。
