TPGS修饰的紫杉醇pH敏感脂质体处方优化及制剂学性质的考察

发布时间：2018-04-09 01:23

本文选题：紫杉醇　切入点：生育酚聚乙二醇琥珀酸盐　出处：《沈阳药科大学学报》2017年03期

【摘要】：目的筛选生育酚聚乙二醇琥珀酸盐(tocopheryl polyethylene glycol 1000 succinate,TPGS)与紫杉醇(paclitaxe,PTX)的质量比例,对TPGS修饰的PTX p H敏感脂质体进行处方优化及制剂学性质的考察。方法采用噻唑蓝(methyl thiazolyl tetrazolium,MTT)法以逆转耐药为指标筛选TPGS与PTX的质量比;采用薄膜分散法制备脂质体,对制剂进行单因素考察,并以包封率、载药量和24 h稳定性(24 h包封率和24 h载药量)为指标,应用星点设计-效应面法对处方及工艺进行优化。测定脂质体的粒径、Zeta电位和体外释药行为。结果 TPGS与PTX的最优质量比例为1:1,制剂的最优处方和工艺确定为m(dioleoyl phosphoethanolamine,DOPE):m(cholesteryl hemisuccinate,CHEMS):m(hydrogenated soybean phospholipids,HSPC)=6:4:2,m(TPGS):m(PTX)=1:1,投药量:1.02 mg,水化时间:12.29 min,水化温度:35℃,超声条件:200 W,5 min。脂质体的包封率为83.54%,载药质量分数为6.52%,24 h包封率和载药质量分数分别为80.03%和5.97%,稳定性良好。脂质体粒径为(115.8±2.03)nm,Zeta电位为(-56.47±1.55)m V。在p H 5.0条件下脂质体释药速率明显增加。结论星点设计成功实现了对处方的优化,且模型预测性良好;最优处方制备的脂质体具有较高的包封率和载药量,粒径较小且分布均匀,体外释放表现出一定的p H敏感性。
[Abstract]:Objective to screen the mass ratio of tocopheryl polyethylene glycol 1000 succinate glycol 1000 and paclitaxel PTXs modified by TPGS and to optimize the formulation of TPGS modified PTX pH-sensitive liposomes.Methods the mass ratio of TPGS to PTX was screened by methyl thiazolyl thiazolyl tetrazolium MTT, and liposomes were prepared by thin-film dispersion method.The method of star design-effect surface method was used to optimize the prescription and process.The particle size and Zeta potential of liposomes and drug release behavior in vitro were measured.The entrapment efficiency of liposome was 83.54 and the mass fraction of drug loading was 6.52%. The entrapment efficiency and drug loading mass fraction of liposome were 80.03% and 5.97% in 24 h, respectively. The stability of liposome was good.The particle size of liposome was 115.8 卤2.03nmGV, the Zeta potential was 56.47 卤1.55mV.The release rate of liposomes increased significantly at pH 5.0.Conclusion the formulation was optimized successfully by star design and the model was predictable. The liposomes prepared by the optimal formulation had higher encapsulation efficiency and drug loading, smaller particle size and uniform distribution, and showed a certain sensitivity to pH release in vitro.
【作者单位】：沈阳药科大学药学院;
【分类号】：R943

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