【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-LCTSLs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10mg/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%.更多还原

【Abstract】 OBJECTIVE To prepare fluorouracil loaded long-circulating thermo-sensitive liposomes. METHODS 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-LCTSLs,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 was9.2∶1,the concentration of fluorouracil rehydration solution was 10 mg/mL and the organic phase and the aqueous phase volume ratio was 7∶1. The entrapment efficiency of optimal formulation was40.85%,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,cumulative release rate of FU-LCTSLs was less than 10% after 30 min 37 ℃ water bath,however,the value was more than 95% after 8 min 42 ℃ water bath. The optimal FU-LCTSLs exhibited good stability. Passing through 0.22 um filter membrane,dilutting by water for injection or 5% glucose solution 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%.更多还原