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通过共喷雾干燥胸膜肺炎放线杆菌抗原和乙基纤维素水分散体制备的微球的释放特性

Release characteristics of microspheres prepared by co-spray drying Actinobacillus pleuropneumoniae antigens and aqueous ethyl-cellulose dispersion.

作者信息

Liao C W, Cheng I C, Yeh K S, Lin F Y, Weng C N

机构信息

Department of Pathobiology, Pig Research Institute Taiwan, Chu-Nan, Miaoli, Republic of China.

出版信息

J Microencapsul. 2001 May-Jun;18(3):285-97. doi: 10.1080/02652040010019442.

Abstract

Using formalin inactivated Actinobacillus pleuropneumoniae antigens and aqueous ethylcellulose dispersions, microspheres of oral vaccines were developed by a co-spray drying process. The present study attempted to determine whether the dosage formulations of microspheres could form enteric matrices. To assess the enteric characteristics, an in vitro dissolution test was performed with the AQ6-AP microspheres; 95% of the A. pleuropneumoniae protein was released within 3 h at pH 7, but there was no release at pH 1.5. The scanning microscopy revealed that the surface structure of AQ6-AP microspheres became porous at neutral pH. The SDS-PAGE analysis showed that the release rate of proteins from the microspheres was pH dependent not only for the AQ6-AP formulation but also when antigens of A. pleuropneumoniae were replaced with porcine serum. The results suggest that the A. pleuropneumoniae antigens were entrapped in the AQ6 microspheres under the acidic conditions. In a mouse model, oral immunization with AQ6-AP microspheres containing A. pleuropneumoniae evoked systemic IgG and mucosal IgA responses against A. pleuropneumoniae antigens. Thus, the present method may further provide an opportunity to develop oral vaccines and mucosal immunity.

摘要

利用福尔马林灭活的胸膜肺炎放线杆菌抗原和乙基纤维素水分散体,通过共喷雾干燥工艺制备了口服疫苗微球。本研究试图确定微球的剂型是否能形成肠溶基质。为评估肠溶特性,对AQ6-AP微球进行了体外溶出试验;在pH 7时,95%的胸膜肺炎放线杆菌蛋白在3小时内释放,但在pH 1.5时无释放。扫描显微镜显示,AQ6-AP微球在中性pH下表面结构变得多孔。SDS-PAGE分析表明,不仅AQ6-AP制剂,而且当胸膜肺炎放线杆菌抗原被猪血清替代时,微球中蛋白质的释放速率都依赖于pH。结果表明,胸膜肺炎放线杆菌抗原在酸性条件下被包裹在AQ6微球中。在小鼠模型中,用含胸膜肺炎放线杆菌的AQ6-AP微球进行口服免疫可引发针对胸膜肺炎放线杆菌抗原的全身性IgG和黏膜IgA反应。因此,本方法可能进一步为开发口服疫苗和黏膜免疫提供机会。

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