氨基蝶呤修饰的蒿甲醚脂质体的制备工艺研究

Preparation and characterization of APGA modified artemether liposomes

目的优选氨基蝶呤修饰的蒿甲醚脂质体的最佳处方配比和制备工艺,并进行理化性质评价。方法以包封率为指标,优选氨基蝶呤修饰蒿甲醚脂质体的制备方法,并通过正交试验优化其处方及工艺;采用激光粒度仪、透射电镜评价脂质体的粒径、Zeta电位及外观形态;利用透析法研究脂质体的体外释放。结果制备的氨基蝶呤修饰的蒿甲醚脂质体的最优处方为卵磷脂-胆固醇-TPGS物质的量比95∶0.5∶3,5%氨基蝶呤修饰率,蒿甲醚与脂材的比例为1∶20,30℃下旋转成膜,水化后,探头超声8 min。所得的氨基蝶呤修饰蒿甲醚脂质体的粒径为(99.97±1.67)nm;多分散度为0.185±0.021;Zeta电位为(-0.023±0.080)m V。透射电镜结果显示蒿甲醚脂质体形态圆整;包封率为(90.06±1.15)%;在模拟血液中,蒿甲醚脂质体的48 h累积释放率为(57.07±6.09)%。结论正交试验优选的氨基蝶呤修饰的蒿甲醚脂质体形态圆整、粒径小且均一、药物包封率较高、具有很好的缓释效果。

Objective To optimize the formulation ratio and preparation process of the APGA modified artemether liposomes,and evaluate its physical and chemical properties.Methods The encapsulation efficiency of artemether was evaluated as index,and the preparation method of APGA modified artemether liposomes was optimized.The preparation process of APGA modified artemether liposomes was optimized by orthogonal experiments.Laser particle analyzer and transmission electron microscopy were used to evaluate the particle size,Zeta potential,and appearance of liposomes,and dialysis method was used to study the release of liposomes in vitro.Results The best prescription was as follow:EPC-Chol-TPGS at 95∶0.5∶3,5%APGA-PEG-DSPE,the artemether-lipid ratio at 1∶20,film-forming temperature 30℃,probe ultrasound time 8 min.The resulting liposomes exhibited a pale blue opalescent appearance.The average particle size,polydispersity index,and zeta potential of artemether liposomes was(99.97±1.67)nm,0.185±0.021,and(-0.023±0.080)m V,respectively.Transmission electron micrograph image showed that artemether liposomes were spherical vesicles with uniform sizes.The encapsulation efficiency of artemether in liposomes was(90.06±1.15)%.In vitro cumulative release rate of artemether from the liposomes in the simulated body fluids was(57.07±6.09)%after 48 h.Conclusion The optimized APGA modified artemether liposomes was successfully developed.It had the following characters:round shape,uniform particle size,high drug encapsulation efficiency and good sustained-release effect.