[关键词]
[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、27.59 μmol/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。
[Key word]
[Abstract]
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 19.41 μmol/L, while L02 was 27.59 μmol/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.
[中图分类号]
R283.6
[基金项目]
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)