包载缺氧诱导因子-1α反义寡核苷酸纳米粒子的制备和特性评价  

Preparation and characterization of hypoxia-inducible factor-1α antisense oligonucleotide loaded nanoparticles

作　　者：郑延波[1] 刘胜[1] 李丽君[1] 刘万卉[2] 

机构地区：[1]烟台毓璜顶医院介入放射科,山东烟台264000 [2]烟台大学药学院,山东烟台264000

出　　处：《生物医学工程与临床》2011年第6期579-583,共5页Biomedical Engineering and Clinical Medicine

基　　金：山东省医药卫生科技发展计划项目(2007HW015)

摘　　要：目的制备一种包载缺氧诱导因子-1α(HIF-1α)反义寡核苷酸的聚乳酸-聚乙醇酸共聚物(PLGA)纳米粒子,并评价其理化特性。方法应用复乳化-溶剂挥发法制备包载HIF-1α反义寡核苷酸PLGA纳米粒子,并固定其他因素,选择不同的聚乙烯醇(PVA)浓度(0.5%、1.0%、1.5%、2.0%)和乳化速度(17 500、21 500、24 000 r/min),观察其对制备的纳米粒子粒度和载药量的影响;应用电子显微镜和粒度测定仪对制得的纳米粒子进行形态观察和粒径测定;应用高效液相色谱法测定纳米粒子的载药量和包封率并进行体外释药实验。结果制得的载HIF-1α反义寡核苷酸PLGA纳米粒子外观呈圆形或介于圆形与椭圆形之间,表面光滑圆整,粒径分布范围较窄,平均粒度为320 nm(标准差50 nm),纳米粒子载药量为(0.930±0.015)%,包封率为(79.14±1.78)%;纳米粒子中HIF-1α反义寡核苷酸在24 h突释期内累积释放率为31.2%,10 d内呈缓慢线性稳定性释放,释放量达81.5%。结论应用复乳化-溶剂挥发法制备包载HIF-1α反义寡核苷酸PLGA纳米粒子,方法实用有效,工艺稳定,重复性好。Objective To prepare and characterize the hypoxia-inducible factor-1α antisense oligodeoxynucleotide（HIF-1α-ASODN） loaded nanoparticles.Methods Biodegradable polylactide-co-glycolide（PLGA） was used as the carrier material to prepare HIF-1α-ASODN loaded nanoparticles using the emulsification/solvent evaporation technique.The effects of polyvinyl alcohol（PVA） concentration and emulsion speed on drug loading and diameter of nanoparticles were observed.The morphology and size of the nanoparticles were measured by scanning electron microscope and granularity calcimeter,respectively.The drug loading and embedding rates,as well as the in vitro drug release characteristic were investigated with high performance liquid chromatography.The physical stability of the nanoparticles and amplified fragment length polymorphism（AFLP） suspension was observed by naked eye and microscope.Results The HIF-1α-ASOND loaded PLGA nanoparticles were of uniform spherical or oval shape,with mean diameter of（320 ± 50） nm.The drug loading efficiency and encapsulation rate of HIF-1α-ASODN nanoparticles were 0.930 % ± 0.015 % and 79.14 % ± 1.78 %,respectively.The in vitro drug release rate was 31.2 % in burst release phase and rose to 81.5 % at the end of the 10th day.Conclusion It is demonstrated that suspension of AFLP with HIF-1α-ASODN loaded PLGA nanoparticles have good physical stabilities,and the emulsification/solvent evaporation technique employed for preparing HIF-1α-ASODN loaded PLGA nanoparticles was stable,effective,and reproducible.

关 键 词：缺氧诱导因子-1Α 反义寡核苷酸 纳米粒子 聚乳酸-聚乙醇酸共聚物 

分 类 号：R318.08[医药卫生—生物医学工程]