叶酸受体靶向伊马替尼pH敏感脂质体的制备工艺及质量评价研究  

Preparation and Evaluation of Folate Receptor-targeted pH-Sensitive Imatinib Liposomes

作　　者：叶鹏[1,2] 杨坦[2] 盖永康 项光亚[2] 

机构地区：[1]武汉大学人民医院药学部,武汉430060 [2]华中科技大学同济医学院药学院

出　　处：《中国药师》2016年第8期1473-1478,共6页China Pharmacist

基　　金：国家自然科学基金项目(编号:81503015)

摘　　要：目的:运用改良的硫酸铵梯度法制备叶酸受体靶向伊马替尼pH敏感脂质体(FSLI),并评价其质量。方法:采用改良的硫酸铵梯度法制备FSLI,以包封率为指标进行制备工艺的优化;采用琼脂糖凝胶CL-4B柱分离脂质体和游离药,HPLC法测定FSLI的包封率;运用Zeta PALS粒径电位分析仪测定脂质体的平均粒径及Zeta电位,透射电镜观察脂质体的形态;运用动态透析法考察FSLI在不同pH环境中的药物释放情况,并考察FSLI在不同pH、37℃水浴中的粒径随时间的变化情况。结果:制得的FSLI为圆形或类圆形的大单室脂质体,平均粒径为(155.2±1.92)nm,Zeta电位为-(29.36±3.21)mV,平均包封率为(90.7±1.70)%。FSLI在pH 7.4的中性环境中药物释放缓慢24 h累积释放度为2.76%而在pH 5.5的酸性环境中药物释放显著加快24 h累计释放度均达到93.2%表现出非常强的pH敏感性能。FSLI在pH 7.4的中性环境中不具有融合性能而在pH 5.5的酸性环境中粒径迅速增大脂质体发生融合。结论:采用改良硫酸铵梯度法制备的FSLI,能获得较高的包封率,并具有良好的pH敏感性能。Objective： To prepare folate receptor-targeted（ FR-targeted） p H-sensitive imatinib liposomes（ FSLI） by an ammonium sulfate gradient method with minor modification and evaluate the quality. Methods： FSLI were prepared by an ammonium sulfate gradient method with minor modification. The optimization of preparation process was accomplished by determining the entrapment efficiency of FSLI. The liposomes and free drugs were separated by a Sepharose CL-4B column and the entrapment efficiency of FSLI was determined by HPLC. The shape,particle size and zeta potential of FSLI were investigated by a transmission electron microscope and a laser scatter,respectively. The drug release and the change of particle size of FSLI at different p H environments were studied by a dynamic dialysis method. Results： FSLI were round or oval large unilamellar vesicles with the average particle size of（ 155. 2 ± 1. 92）nm. The zeta potential was-（ 29. 36 ± 3. 21） m V and the entrapment efficiency was（ 90. 7 ± 1. 70） %. FSLI released slowly at the neutral environment with p H of 7. 4,and the cumulative release rate was 2. 76% in 24 h. FSLI released fast at the acidic environment with p H of 5. 5,and the cumulative release rate was 93. 2% in 24 h. FSLI showed notably p H sensitive property. FSLI didn＇t integrate at the neutral environment,while integrated at the acidic environment resulting in the rapid increase of particle size. Conclusion： FSLI prepared by the ammonium sulfate gradient method with minor modification are with high entrapment efficiency and remarkable p H sensitivity.

关 键 词：伊马替尼 PH敏感 脂质体 叶酸受体靶向 

分 类 号：R944.9[医药卫生—药剂学]