反义寡核苷酸聚氰基丙烯酸丁酯纳米粒的制备及载药研究  

Study on preparation of antisense oligodeoxynucleotides-loaded polybutylcyanoacrylate nanoparticles and its load-ing

作　　者：刘伟[1] 张红岭[1] 周天洋[1] 厉留柱[2] 严瑛[1] 毛陆原[2] 张振中[1] 

机构地区：[1]郑州大学药学院,河南郑州450052 [2]郑州大学材料工程学院,河南郑州450052

出　　处：《中国药学杂志》2005年第17期1312-1315,共4页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目(30371695)

摘　　要：目的制备载反义寡核苷酸(ASODNs)聚氰基丙烯酸丁酯阳离子纳米粒。方法以二乙氨乙基-葡聚糖(DEAE-Dextran)为修饰剂,采用乳化聚合法制备阳离子聚氰基丙烯酸丁酯纳米粒,采用吸附法制备载ASODNs纳米粒。用原子力显微镜观察其形态,用激光粒度仪测定Zeta电位及粒径,高效液相法测定药物的载药量和包封率,琼脂糖电泳分析抗核酸酶的能力。结果制得的纳米粒(NP),形态规整、大小均匀,平均粒径为90.2nm,Zeta电位值为+40.1mV,载药量达到84.3μm·mg-1时,几乎所有的药物被负载,DEAE-Dextran-(NP)所吸附的ODNs有较好的对抗核酶降解的能力。结论DEAE-Dextran-NP是一种稳定、高效的反义寡核苷酸传递系统。OBJECTIVE To prepare antisense oligodeoxynueleotides-loaded polybutyleyanoa-erylate nanoparticles.METHODS The cationic polybutylcyanoacrylate nanoparticles were prepared by an emulsion polymerization process with the presence of DEAE-Dextran. Antisense oligodeoxynucleotides were loaded on the particles by adsorption. The morphology was inve-stigated by atomic force microscopy. The size and surface charge of the nanoparticles were determined by laser particle analyter. The entrapment efficiency and loading were determined by HPLC. The ability of protecting oligodeoxynucleotides from enzyme attack was investigated on a agamse gel. RESULTS The resulting nanopartieles had regular spherical surface. A narrow particle size distribution with a mean diameter of 90.2 nm,a high Zeta potentials of ＋ 40.1 mV and a high-oligodeoxynucleotides-loading of 84.3 μg· mg^- 1 were obtained. Most of the antisense oligodeoxynucleotides was loaded. The oligodeoxynueleotides botmd to these nanopartieles were found to be protected from DNase attack. CONCLUSION The cationic polybutyleyanoacrylate nanopartieles appear to be a promising vehicle for antisense oligodeoxynueleotides.

关 键 词：聚氰基丙烯酸丁酯 纳米粒 反义寡核苷酸 传递系统 

分 类 号：R943[医药卫生—药剂学]