摘要
目的:碱裂解法提取编码胆固醇酯转运蛋白的质粒(简称pCETP)作为核酸疫苗,并制成适合鼻腔递送的载核酸疫苗壳聚糖纳米冻干剂。方法:碱裂解法大量提取抗动脉粥样硬化核酸疫苗,以壳聚糖(简称CS)为非病毒载体,复凝聚法制备pCETP/CS纳米粒,正交设计筛选最佳pCETP/CS纳米冻干剂处方。结果:提取了纯度可靠的pCETP,制得的pCETP/CS冻干剂具有较高的包封率(94.6%)和载药量(27.3%),重分散后纳米粒粒径为(375±18)nm,pCETP浓度可达4000μg.mL-1,较冻干前提高40倍。结论:pCETP/CS冻干剂具有良好的稳定性和重分散性,为适合鼻内递送的载基因微粒制剂,具有较好的研究前景。
Objective: The plasmid encoding cholesterol ester transfer protein (pCETP) extracted by alkaline lysis approach, was used to prepare pCETP/Chitosan(CS) lyophilized nanopartieles for nasal mucosa administration. Methods: Alkaline lysis method was used for extracting pCETP as antiatheroselerosis DNA vaccine. The pCETP loaded chitosan nanoparticles were prepared by the complex eoacervation method. Results: The obtained purity of pCETP was reliable. By the orthogonal design, the optimized freeze-drying formulation led to high encapsulating efficiency(94.6%) and drug-loading content(27.3%). The size of the redispersed nanoparticles was (375±18)nm, and the concentration of pCETP was as high as 4000μg·ml^-1. Furthermore, the volume of the administration was reduced as much as 40 fold, compared with the volume before freeze-drying. Conclusion: The pCETP/CS freeze-dried complex with good stability and redispersibility is a potential immunization formulation for nasal mucosa administration and worthy for further exploitation.
出处
《药学与临床研究》
2011年第2期107-111,共5页
Pharmaceutical and Clinical Research
基金
国家自然科学基金(No.30572272)