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用于出血性败血症疫苗的多杀巴斯德氏菌负载微粒的研制

Development of Pasteurella multocida-loaded microparticles for hemorrhagic septicemia vaccine.

作者信息

Nimtrakul Pataranapa, Atthi Ratchanee, Limpeanchob Nanteetip, Tiyaboonchai Waree

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University , Phitsanulok , Thailand .

出版信息

Drug Dev Ind Pharm. 2015 Mar;41(3):423-9. doi: 10.3109/03639045.2013.873448. Epub 2013 Dec 31.

DOI:10.3109/03639045.2013.873448
PMID:24378199
Abstract

In this study, Pasteurella multocida-loaded alginate microparticles (MPs) for subcutaneous vaccination was developed by emulsification-cross-linking technique. Formulation parameter was varied as a ratio of polymer and bacterin. Optical microscopy revealed spherical particles with uniformly distribution. A mean particle size of approximately 6 µm has been successfully constructed using simple mixer and ultrasonic probe. The zeta potential of the MPs showed negatively charge of approximately -23 mV determined by Zeta Pals® analyzer. The entrapment efficiency and the in vitro bacterin released profile could be controlled by varying the amount of alginate. The high entrapment efficiency up to 69% was achieved with low concentration of alginate. The MPs possessed a slow bacterin release profile, up to 30 days. In vivo safety and potency tests were proved that the alginate MPs were safe and induced protective immunity in mice. In addition, after storage for 6 months at either 4 °C or room temperature, the protective immunity in mice was maintained.

摘要

在本研究中,通过乳化交联技术制备了用于皮下接种的载多杀巴斯德菌藻酸盐微粒(MPs)。制剂参数随聚合物与菌苗的比例而变化。光学显微镜显示为球形颗粒,分布均匀。使用简单混合器和超声探头成功构建了平均粒径约为6μm的微粒。通过Zeta Pals®分析仪测定,MPs的ζ电位显示约为-23mV的负电荷。通过改变藻酸盐的量可以控制包封率和体外菌苗释放曲线。低浓度藻酸盐可实现高达69%的高包封率。MPs具有缓慢的菌苗释放曲线,长达30天。体内安全性和效力测试证明藻酸盐MPs在小鼠中是安全的,并能诱导保护性免疫。此外,在4℃或室温下储存6个月后,小鼠的保护性免疫得以维持。

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