枸橼酸二甲双胍阿霉素脂质体的制备

Preparation of citral metformin doxorubicin liposomes

目的制备二甲双胍阿霉素脂质体并对其制备工艺进行优化。方法以二甲双胍阿霉素脂质体的包封率为评价指标,对其处方和制备工艺进行筛选和优化。分别考察了磷脂与胆固醇的比例、水化介质中阴离子的种类、水化介质的浓度、水化介质的pH值、载药温度、载药时间对二甲双胍阿霉素脂质体包封率的影响。结果最终优化的处方为m(hydrogenated soybean phosphatidylcho-line,HSPC)∶m(cholesterol,CH)∶m(polyethylene glycol 2000-cholesteryl hemisuccinate,mPEG2000-CHEMS)=3.0∶1.0∶1.0,以pH为7.00的300 mmol.L-1的枸橼酸二甲双胍为水化介质,60℃载药60 min,所制备的脂质体包封率可达98.7%。结论以枸橼酸二甲双胍离子梯度法制备的阿霉素脂质体包封率高,方法可行。

Objective To prepare metformin-doxorubicin liposomes and optimize the method of preparation.Methods The mixed ion exchange resin method was used to establish transmembrane ion gradient of citrate-metformin and prepare metformin-doxorubicin liposomes,the method of preparation process and formulation factors were investigated with comparison of different anions on encapsulation efficiency of liposomes.Results The optimal formulation of DOX liposome was m（hydrogenated soybean phosphatidylcholine,HSPC）∶ m（cholesterol,CH）∶ m（polyethylene glycol 2000-cholesteryl hemisuccinate,mPEG2000-CHEMS）=3.0∶ 1.0∶ 1.0,the concentration of（MetH）3CA was 300 mmol · L-1 with pH value of 7.00,loading temperature was 60 ℃,loading time was 60 min.The encapsulation efficiency of doxorubicin liposomes increased to 98.7%.Conclusions The metformin-doxorubicin liposomes with high entrapment efficiency are prepared by the citrate-metformin ion gradient method,the method is proved to be feasible