界面聚合法制备反义核酸氰基丙烯酸正丁酯纳米粒的研究及稳定性考察  

Preparation of antisense oligodeoxynucleotides-loaded butylcyanoacrylate nanoparticles by interfacial polymerization and their stability

作　　者：徐越[1] 柯以铨[1] 杨西晓[2] 阎玺庆[3] 王建奇[1] 黄乐松[2] 

机构地区：[1]南方医科大学珠江医院神经外科,广州510282 [2]南方医科大学：南方医院药学部,广州510515 [3]南方医科大学：深圳清华大学研究院中药中心,广东深圳518057

出　　处：《第三军医大学学报》2008年第14期1334-1337,共4页Journal of Third Military Medical University

基　　金：广东省自然科学基金(05004763)~~

摘　　要：目的优化制备包裹反义寡核苷酸a-氰基丙烯酸正丁酯纳米粒(ASODN in NP)并考察稳定性。方法以氰基丙烯酸正丁酯(butyleyanoacrylate,BCA)为载药材料,采用界面聚合法制备ASODN in NP;在单因素考察的基础上,采用正交设计优化处方和制备工艺;用透射电镜观察其形态;马尔文激光粒度分析仪测定粒径;高效液相色谱法测定载药量和包封率;用含7mol/L尿素的20%聚丙烯酰胺凝胶电泳考察载药纳米粒在体外血清中的稳定性。结果按优化工艺条件,制得的载药纳米粒,其形态规整、无黏连、大小均匀,平均粒径为94.9nm,包封率和载药量分别为96.7%、10.1%,在体外血清中稳定性好并优于传统的吸附法制备的纳米粒。结论本实验制备的ASODN in NP具有较好的稳定性,较高包封率和载药量。Objective To optimize the preparation of nanoparticles encapsulating antisense oligodeoxynucleotides in a-butyleyanoacrylate carrier （ASODN in NP） and investigate their stability. Methods ASODN in NP were prepared by interfacial polymerization of butyleyanoacrylate （BCA）. The formulation and technology of the prepared NP was optimized by using orthogonal design based on the single-factor experiment. The morphology of NP was examined by transmission electron microscope; The size and size distribution of NP were determined by Malvern laser granularity equipment ;The encapsulation efficiency and drug loading were determined by HPLC; The ability of protecting oligodeoxynucleotides from serum was inv ide-7 Murea sequencing gel （PAGE）. Results The nanoparticles in the o estigated on a 20% polyacrylamptimal conditions were of regular spherical surface and discrete. The average size was 97.1 nm, the average encapsulation efficiency and drug loading of ASODN in NP were 96.7% and 10.1% respectively; The oligonucleotides were more efficiently protected from degradation by nucleases than by oligonucleotides adsorbed into nanospheres. Conclusion ASODN in NP has good stability, encapsulation efficiency,drug loading and great potential for ASODN delivery.

关 键 词：反义寡核苷酸 氰基丙烯酸正丁酯 纳米粒 稳定性 界面聚合法 

分 类 号：R943[医药卫生—药剂学] R944.9[医药卫生—药学]