Box-Behnken结合响应面法优化制备氟尿嘧啶长循环热敏脂质体  

Optimization of Fluorouracil Loaded Long-circulating Thermo-sensitive Liposomes by Box-Behnken Design and Responsed Surface Method

作　　者：吴义来 汪魏平[1] 徐文科[1] WU Yi-lai;WANG Wei-ping;XU Wen-ke(Dept. of Pharmacy,The First Affiliated Hospital of Wannan Medical College,Wuhu,Anhui 241001,China)

机构地区：[1]皖南医学院弋矶山医院药学部

出　　处：《通化师范学院学报》2019年第8期52-59,共8页Journal of Tonghua Normal University

基　　金：皖南医学院中青年科研基金项目(WK2016F09)

摘　　要：目的:优化制备氟尿嘧啶长循环热敏脂质体.方法:运用Box-Behnken试验设计结合响应面法(BBD-RSM)以包封率为评价指标优化FU-LCTSLs的处方和制备工艺.考察按最优处方制备的FU-LCT-SLs的理化性质,包括外观、粒径分布、Zeta电位、pH值和体外热敏释放实验,并对FU-LCTSLs进行稳定性研究.结果:经优化得到最优处方为脂质体膜材与氟尿嘧啶的质量比9.2:1,水化液中氟尿嘧啶的浓度10 mg/mL,有机相与水相的体积比7:1.按此处方工艺制备的脂质体包封率40.85%,粒径113.7±8.7 nm,PDI=0.538±0.072,Zeta电位-15.34±4.26 mV,pH值7.35±0.04,温度敏感性良好,37℃下30 min累积释药率小于10%,42℃下8 min累积释药率大于95%.稳定性良好,0.22 um微孔滤膜过滤、注射用水或5%葡萄糖稀释对FU-LCTSLs包封率影响不大,4℃保存6个月渗漏率仅2.86%.OBJECTIVE To prepare fluorouracil loaded long-circulating thermo-sensitive liposomes.METH.ODS Entrapment efficiency was used as an index to evaluate preparing methods and formulas by Box-Behnken design and responsed surface method.The physicochemical properties of FU-LCT.SLs,including appearance,particle size distribution,zeta potential,pH,in vitro thermo-sensitive release behavior were investigated.FU-LCTSLs stability studies were also conducted.RESULTS The best entrapment efficiency was obtained when mass ratio of phospholipid to fluorouracil was 9.2∶1,the concentration of fluorouracil rehydration solution was 10mg/mL and the organic phase and the aqueous phase volume ratio was 7∶1.The entrapment efficiency of optimal formulation was 40.85%,Particle size was 113.7±8.7 nm,PDI was 0.538±0.072,Zeta potential was-15.34±4.26 mV,pH value maintained at 7.35±0.04.Excellent temperature sensitivity was observed,cumula.tive release rate of FU-LCTSLs was less than 10% after 30 min 37 ℃ water bath,however,the val.ue was more than 95% after 8min 42 ℃ water bath.The optimal FU-LCTSLs exhibited good stabil.ity.Passing through 0.22 um filter membrane,dilutting by water for injection or 5% glucose solu.tion generated little effect on the encapsulation efficiency of FU-LCTSLs.FU-LCTSLs maintained more stable when preserved under 4 ℃,the leakage after 6 months preservation was 2.86%.

关 键 词：Box-Behnken 响应面法 优化制备 氟尿嘧啶 长循环 热敏脂质体 

分 类 号：R285.5[医药卫生—中药学]