摘要
目的:通过考察幽门螺杆菌(Helicobacter pylori,Hp)微球生物学行为,探讨其作为口服蛋白疫苗的可行性。方法:用可降解天然高分子材料-壳聚糖和海藻酸钠制备Hp全菌蛋白微球(HpWCP-CAMS),通过BCA方法测定微球中蛋白质的包裹效率及包裹量,测定微球在体外的药物释放度。并进行小鼠体内微球的靶向试验,微球的体内外毒性试验和淋巴细胞致敏试验。结果:HpWCP-CAMS中蛋白包裹量为31.5%,蛋白包裹效率为61.0%。微球中药物缓释周期可长达20 d,靶向试验结果显示微球能在肠黏膜、PP结及脾脏富集并能有效诱导淋巴细胞致敏。体外毒性显示125μL微球(5 mg.mL-1)对Hela细胞生长无明显影响,体内实验结果显示其对小鼠生长也没有影响。结论:HpWCP-CAMS具有良好的靶向性和缓释特征,无细胞毒性,有望作为疫苗进一步研究。
Objective: To study the feasibility of Helicobacter pylori(Hp) microsphere used as an oral vaccine. Methods: Used the biodegradable polymers chitosan and sodium alginate as carrier matrixes, a Hp WCP-CAMS (whole cell protein-chitosan-alginate microsphere ) was prepared by iso-project method. The entrapment rate and quantity of the protein loaded in the microspheres were measured by a BCA test. Other features including the dissolution rate in vitro, targeting delivery to tissues in vivo, toxicities and lymphocyte sensitization in vitro and in vivo of mice were determined. Results:The HpWCPCAMS characterized an entrapment rate of the protein of 61.0%, the loading quantity of the protein of 31.5%, the sustained release rate of 20 days, and the targeting delivery toward intestinal mucosa, peyer's patch and spleen. No toxicity of Hela cells in vitro and inhibition of the mice found by the microspheres 125μL (5 mg·mL^-1). Conclusion: The Helicobacter growth in vivo were pylori microspheres showed a targeted and sustained release and safety profile, which has the potential for further investigations to be used as the Oral vaccine.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2007年第7期539-543,共5页
Chinese Journal of New Drugs
基金
国家"十五"863课题(2001AA215161
2003AA215020)
关键词
微球疫苗
幽门螺杆菌
包封率
药物释放度
毒性试验
microsphere vaccine
Helicobacter pylori
entrapment rate
drug release
toxicity