载As2O3 pH敏感钙砷复合物脂质体的制备及体外评价  

Preparation and in vitro evaluation of pH-sensitive drug releasing As2O3-loadedliposome

作　　者：陈云云 姚文栋 谢先泽 毛超 张钶 诸佳珍[2] CHEN Yun-yun;YAO Wen-dong;XIE Xian-ze;MAO Chao;ZHANG Ke;ZHU Jia-zhen(Department of Pharmacy,The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310018,China;Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学附属第一医院药剂科,浙江杭州310018 [2]浙江中医药大学,浙江杭州310053

出　　处：《中草药》2020年第21期5447-5453,共7页Chinese Traditional and Herbal Drugs

基　　金：浙江省中医药优秀青年人才基金项目(2018ZQ013);浙江省自然科学青年基金项目(LQ19H280004);浙江中医药大学2018年度校级科研基金资助项目(2018ZJ09)。

摘　　要：目的制备pH敏感释药的As2O3脂质体,并进行体外评价。方法采用薄膜分散法制备含钙离子脂质体,然后用离子沉淀法孵育制备钙砷复合物脂质体(CaAs-LP)。测定CaAs-LP的粒径、Zeta电位及多分散系数(PDI);透射电子显微镜观察脂质体的形态;电感耦合等离子体发射光谱仪测定纳米药物的载药量与包封率;透析袋法考察其体外释药特性。噻唑蓝(MTT)法考察未载药脂质体及CaAs-LP对人源性乳腺癌MCF-7细胞、人源性脑胶质瘤U87细胞和人源性肝癌HepG2细胞的毒性;共聚焦显微镜考察U87细胞对CaAs-LP的摄取效率。结果制备的CaAs-LP呈规整类球型,粒径约为(117.16±1.94)nm,包封率和载药量分别为(74.31±2.11)%、(8.31±0.13)%。体外释放研究表明,CaAs-LP具有明显的缓释以及pH响应释药特征。未载药的脂质体在MCF-7、U87、HepG2和L02细胞中的生物相容性良好;CaAs-LP抑制肿瘤细胞生长的作用较原药有所上升,半数抑制浓度(IC50)值分别为11.91、4.90、19.41、27.59μmol/L。细胞摄取研究表明肝癌细胞对脂质体具有良好的摄取。结论CaAs-LP具备显著的缓释以及pH响应释药的特性,在肿瘤治疗方面具有较好的应用前景。Objective To prepare pH-sensitive drug releasing As2O3 loaded liposome(CaAs-LP)and evaluate it in vitro.Methods CaAs-LP was prepared by thin film dispersion and ion precipitation method.The particle size,PDI,and Zeta potential of CaAs-LP were measured by Malvern particle size analyzer;The morphology of the liposome was investigated by transmission electron microscopy;The drug loading and entrapment efficiency of CaAs-LP by inductively coupled plasma emission spectrum.In vitro release characteristics of CaAs-LP under different pH conditions were investigated by dialysis bag method.MTT assay was used to investigate the toxicity of carrier and CaAs-LP to MCF-7,U87 and HepG2 cells.Results The prepared CaAs-LP were spherical and well-dispersed with particle size of(117.16±1.94)nm.The encapsulation efficiency and the drug loading rate of CaAs-LP were(74.31±2.11)%and(8.31±0.13)%,respectively.In vitro release studies showed that CaAs-LP had the characteristics of sustained release and pH sensitive drug release,which can achieve specific drug release in the tumor environment.The carrier displayed remarkable biocompatibility in MCF-7,U87,HepG2 and L02 cells.MTT assay showed that the median lethal concentrations(IC50 values)of MCF-7,U87 and HepG2 cells were 11.91,4.90 and 19.41μmol/L,while L02 was 27.59μmol/L,respectively,which showed strong inhibiting effect on tumor cells.Conclusion CaAs-LP reveals significantly sustained and pH sensitive release characteristics.CaAs-LP is a potential drug delivery system against solid tumor with tumor micro-environment responsive.

关 键 词：A2O3 脂质体 PH敏感 钙离子 体外评价 薄膜分散法 离子沉淀法 

分 类 号：R283.6[医药卫生—中药学]