超临界反溶剂法制备叶酸介导吡柔比星葡聚糖纳米粒的工艺研究  

Preparation of Folic Acid-conjugated Pirarubicin-loaded Dextran Nanoparticles by Supercritical Antisolvent Method

作　　者：姜茹[1] 祖元刚[1] 赵修华[1] 王丹[1] 祖柏实[1] 孙志强[1] 

机构地区：[1]东北林业大学森林植物生态学教育部重点实验室,哈尔滨市150040

出　　处：《中国药房》2011年第21期1961-1964,共4页China Pharmacy

基　　金：国家林业局"948"项目(2010-4-20);林业公益性行业科研专项(2010040072);东北林业大学研究生论文资助项目

摘　　要：目的:优化可主动靶向癌细胞的叶酸(FA)介导吡柔比星(PRB)葡聚糖(DEX)纳米粒(FA-PRB-DEX-NPs)的制备工艺。方法:采用超临界反溶剂法制备FA-PRB-DEX-NPs,采用二水平设计法,以PRB与DEX质量比(X1)、DEX浓度(X2)、混合液流速(X3)、萃取釜温度(X4)、萃取釜压力(X5)为因素,以粒径、载药量、包封率等为指标筛选出最佳工艺条件,计算叶酸偶联度,通过扫描电镜、红外光谱、X射线衍射分析和差示扫描量热分析法表征纳米粒性质。结果:最佳工艺条件为X1=0.5、X2=9.98mg·mL-1、X3=3.3mL·min-1、X4=50℃、X5=15MPa。以此所制纳米粒的平均粒径、载药量和包封率分别为(178±15.8)nm、7.73%、33.2%,FA偶联度为2.97%。各表征方法结果显示纳米粒与原药比较粒径更小,呈无定形非晶态。结论:筛选的制备工艺成功地制备出了可主动靶向癌细胞表面的FA-PRB-DEX-NPs,且所采用的超临界反溶剂法方法简单,更适合工艺化生产。OBJECTIVE：To optimize the preparation technology of folic acid（FA） -conjugated pirarubicin（PRB） -loaded dextran（DEX） nanoparticles（FA-PRB-DEX-NPs） for tumor-targeted drug delivery. METHODS：Supercritical anti-solvent method was adopted to prepare FA-PRB-DEX-NPs. The ratio of PRB to DEX（X1） ,DEX concentration（X2） ,flow rate of mixture（X3） ,extraction temperature（X4） ,and extraction pressure（X5） as factors and with particle size,drug-loading rate,entrapment efficiency as index were adopted to optimize the preparation technology of FA-PRB-DEX-NPs using two-level factorial design. The coupled conjugate rate of folic acid was calculated and the particles were detected by FTIR,XRD,DSC,SEM. RESULTS：Optimal condition was as follows：X1=0.5,X2=9.98 mg·mL-1,X3=3.3 mL·min-1,X4=50 ℃,X5=15 MPa. Mean particle size,drug-loading rate and entrapment efficiency of nanoparticles were（178±15.8） nm,7.73%,33.2%. The coupled conjugate rate of folic acid was 2.97%. The particle size of nanoparticles was smaller than that of original ones,assumed as amorphous state. CONCLUSION：FA-PRB-DEX-NPs for tumor-targeted drug delivery have been prepared through the supercritical antisolvent method,which is simple and suitable for industrialization.

关 键 词：吡柔比星 葡聚糖 叶酸 超临界反溶剂法 纳米粒 二水平设计法 制备工艺 

分 类 号：R943[医药卫生—药剂学] R979.1[医药卫生—药学]