摘要
目的:通过优化脂质体处方和制备工艺,制备紫杉醇长循环脂质体。方法:采用薄膜分散-挤出法制备长循环脂质体,在处方优化方面,分别以磷脂浓度(X1,mg/m L)、PEG2000-DSPE浓度(X2,mg/m L)和脂药比(X3,W/W)为考察对象,包封率(Y1,%)为评价指标;在制备工艺参数优化方面,以均质温度(X4,℃)、挤出次数(X5,次)为考察对象,粒径分布(Y2,nm)、多分散系数(Y3)为评价指标,利用Box-Behnken效应面法优化紫杉醇长循环脂质体的处方和制备工艺;并测定脂质体的粒径分布、多分散系数及Zeta电位;透射电镜观察其形态,并考察长循环脂质体体外释放行为。结果:紫杉醇长循环脂质体的包封率为80.3%、粒径为(97.15±14.9)nm,多分散系数为0.117±0.019,Zeta电位为(-30.3±3.7)m V;透射电镜显示脂质体粒径均一,呈单层膜球状分布;体外释放试验结果显示在24 h累积释放了37.4%,说明脂质体有一定的缓释作用。结论:紫杉醇长循环脂质体采用Box-Behnken效应面法优化是可行的。
Objective： To develop a procedure for preparing paclitaxel encapsulated PEGylated liposomes. Methods： The membrane hydration followed extraction method was used to prepare PEGylated liposomes. The process and formulation variables were optimized by＂Box-Behnken Design（ BBD） ＂of response surface methodology（ RSM） with the amount of Soya phosphotidylcholine（ SPC） and PEG2000-DSPE as well as the rate of SPC to drug as independent variables and entrapment efficiency as dependent variables for optimization of formulation variables while temperature,pressure and cycle times as independent variables and particle size and polydispersion index as dependent variables for process variables. The optimized liposomal formulation was characterized for particle size,Zeta potential,morphology and in vitro drug release. Results： For entrapment efficiency,particle size,polydispersion index,Zeta potential,and in vitro drug release of PEGylated liposomes was found to be 80. 3%,（ 97. 15 ± 14. 9） nm,0. 117 ± 0. 019,（- 30. 3 ± 3. 7） m V,and37. 4% in 24 h,respectively. The liposomes were found to be small,unilamellar and spherical with smooth surface as seen in transmission electron microscopy. Conclusion： The Box-Behnken response surface methodology facilitates the formulation and optimization of paclitaxel PEGylated liposomes.
出处
《中药材》
CAS
CSCD
北大核心
2015年第12期2606-2610,共5页
Journal of Chinese Medicinal Materials
基金
陕西省重点科技创新团队资助项目(2013KCT-26)
陕西省中药制药重点建设学科资助(10080)
关键词
紫杉醇
长循环脂质体
薄膜分散-挤出
BOX-BEHNKEN效应面法
Paclitaxel
PEGylated liposomes
Membrane hydration followed extraction method
Box-Behnken response surface methodology
