青蒿琥酯脂质体的处方优化及抗非小细胞肺癌评价

Formulation optimization and in vitro antitumor efficacy of artesunate liposomes

目的通过薄膜分散法制备青蒿琥酯脂质体(ART-liposome),并考察其体外抗非小细胞肺癌的活性。方法对磷脂/胆固醇比例和探头超声时间进行筛选,制备ART-liposome并表征其制剂学性质。选择非小细胞肺癌A549细胞为模型,通过细胞毒性、生长状态、摄取情况和染色观察评价ART-liposome的抗肿瘤作用。结果优化后制备的ART-liposome粒径为(120±5.01)nm的球形粒子,分布均一,包封率为(92.45±3.57)%,能够在肿瘤酸性条件下特异性释放药物,累积释放率达到60%。体外细胞实验表明,空白脂质体对细胞几乎没有毒性,具有良好的生物相容性。而ART-liposome能够被细胞较好地摄取以有效地杀死肿瘤细胞。结论ART-liposome是一种有前景的抗肿瘤药物新制剂,可为后续青蒿琥酯的开发提供参考。

Objective To prepare artesunate-loaded liposomes(ART-liposome)by thin film dispersion method and evaluate the in vitro antitumor activity against non-small cell lung cancer.Methods The phospholipid/cholesterol ratio and probe ultrasound time were screened to prepare ART-liposome and determine the pharmaceutical properties.A549 cells,as the model of non-small cell lung cancer cells,were used to verify the antitumor effect of ART-liposome by determining the cytotoxicity,growth status,cellular uptake and staining observation.Results ART-liposome presented uniformly distributed spherical particles of(120±5.01)nm and encapsulation efficacy of(92.45±3.57)%,and specifically released drugs under the acid condition of tumor.In vitro antitumor experiments showed that blank liposomes showed nearly no toxicity to non-small cell lung cancer A549 cells,suggesting good biocompatibility.However,ART-liposome could be uptaken into the tumor cells resulting in effective killing of the tumor cells.Conclusion ART-liposome is a promising new antitumor formula,which provides reference for further research and development of artesunate.