星点设计-效应面法优化低密度脂蛋白纳米粒处方与制备工艺  

Optimization of formulation and preparation process of low density lipoprotein nanoparticle by central composite design-response surface methodology

作　　者：张青[1] 马伟从[1] 张霞[1] 蹇丹[1] 毛声俊[1] 

机构地区：[1]四川大学华西药学院靶向药物及释药系统教育部重点实验室,四川成都610041

出　　处：《华西药学杂志》2013年第1期12-15,共4页West China Journal of Pharmaceutical Sciences

基　　金：国家重大新药创制科技重大专项课题靶向释药系统与新制剂技术平台的建设(立项编号:2009ZX09310-002)

摘　　要：目的研制低密度脂蛋白纳米粒,优选其处方与制备工艺。方法采用薄膜-超声法制备脂微乳,连接含载脂蛋白apoprotein B-100中、低密度脂蛋白受体结合域序列的合成肽制备纳米粒。以脂质浓度、超声功率及超声时间为考察因素,粒径为指标,采用星点设计-效应面法优化其处方及制备工艺。结果优选的脂质浓度为0.1%;超声功率为380 w,超声时间为6 h。制备的纳米粒平均粒径为27.7 nm,PDI为0.17,ζ-电位为-28.7 mV。结论采用星点设计-效应面法优化低密度脂蛋白纳米粒的处方与制备工艺,制备的纳米粒粒径与预测值接近,表明用该法优化其处方与制备工艺可行。OBJECTIVE To prepare the low density lipoprotein（LDL） nanoparticle and optimize its formulation and preparation process.METHODS The film-ultrasonic method was used to prepare lipid microemulsion,and then combined with a synthetic peptide,which contain the LDL receptor（LDLR） binding domain of apoprotein B-100,to obtain the synthetic LDL nanoparticle.Taking the lipid content,ultrasonic power and ultrasonic time as the independent variation,the particle size as the response variable,the central composite design-response surface methodology（CCD-RSM）was applied to optimize the formulation and preparation process of the synthetic LDL nanoparticle.RESULTS The optimal conditions were 0.1% lipid content,380 w ultrasonic power and 6 h ultrasonic time.The mean particle size of LDL nanoparticle prepared according to the optimal conditions 27.7 nm,the PDI value was 0.17 and the ζ-potential was-28.7 mV.CONLUSION A desired particle size of synthetic LDL was obtained according to the CCD-RSM,indicating that the optimized preparation conditions are feasible.

关 键 词：低密度脂蛋白 纳米粒 星点设计―效应面法 处方设计 制备工艺 

分 类 号：R971[医药卫生—药品]