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用于口服递送含皮肤坏死毒素的多杀性巴氏杆菌抗原的粘膜粘附性和pH敏感型巯基化丙烯酸树脂微球。

Mucoadhesive and pH-sensitive thiolated Eudragit microspheres for oral delivery of Pasteurella multocida antigens containing dermonecrotoxin.

作者信息

Islam Mohammad Ariful, Jiang Hu-Lin, Quan Ji-Shan, Arote Rohidas B, Kang Mi-Lan, Yoo Han-Sang, Yun Cheol-Heui, Choi Yun-Jaie, Cho Chong-Su

机构信息

Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, South Korea.

出版信息

J Nanosci Nanotechnol. 2011 May;11(5):4174-81. doi: 10.1166/jnn.2011.3639.

Abstract

In this study, cysteine was conjugated to the Eudragit to have mucoadhesive and pH-sensitive properties. Pasteurella multocida dermonecrotoxin (PMT) is a major virulence factor as a causative agent of atrophic rhinitis (AR) in swine and, therefore, inactivated P. multocida was used as a candidate vaccine in the current study. PMT-loaded thiolated Eudragit microspheres (TEMS) prepared using W/O/W emulsion-solvent evaporation method were characterized to assess their efficacy in oral vaccination. PMT-loaded TEMS were observed as spherical shapes with smooth surfaces and average particle sizes were 5.2 +/- 0.55 microm. The loading efficiency of PMT in the TEMS was about 75.3%. A significantly higher percentage of PMT from PMT-loaded TEMS was released at pH 7.4 than at pH 1.5. Murine macrophage stimulated with PMT-loaded TEMS facilitated a gradual secretion of tumor necrosis factor-alpha and nitric oxide as immune stimulatory mediators in a time dependent manner, suggesting that the released PMT from PMT-loaded TEMS had immune stimulating activity of AR vaccine in vitro.

摘要

在本研究中,半胱氨酸与聚丙烯酸树脂结合以具备粘膜粘附性和pH敏感性。多杀性巴氏杆菌皮肤坏死毒素(PMT)是猪萎缩性鼻炎(AR)病原体的主要毒力因子,因此,灭活的多杀性巴氏杆菌在本研究中被用作候选疫苗。采用W/O/W乳液溶剂蒸发法制备的负载PMT的巯基化聚丙烯酸树脂微球(TEMS)进行了表征,以评估其口服疫苗接种的效果。观察到负载PMT的TEMS呈球形,表面光滑,平均粒径为5.2±0.55微米。PMT在TEMS中的负载效率约为75.3%。负载PMT的TEMS中,在pH 7.4时释放的PMT百分比显著高于pH 1.5时。用负载PMT的TEMS刺激的小鼠巨噬细胞以时间依赖性方式促进肿瘤坏死因子-α和一氧化氮作为免疫刺激介质的逐渐分泌,表明从负载PMT的TEMS中释放的PMT在体外具有AR疫苗的免疫刺激活性。

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