摘  要目的：通过制备脱盐氮芥和氮芥前药双载药胶束，提高氮芥药物的安全性和疗效，为进一步研究高效低毒的氮芥纳米制剂提供依据。方法：制备并采用聚已二醇-环内酯衍生物（PEG-PCCL）作为双载药胶束的载体材料，采用薄膜分散法制备氮芥衍生物双载药胶束；元素分析法法测定药物含量，计算载药量。并使用zeta电位仪测定粒径和电位的大小及分布，并考察室温和4℃条件下PEG-PCCL氮芥衍生物双载药胶束的稳定性。用MTT实验进行K562细胞毒性测定，考察氮芥脱盐前后的细胞毒性变化，筛选PEG-PCCL氮芥衍生物双载药胶束中脱盐氮芥和氮芥前药的适合比例。结果：1H-NMR核磁共振结果表明PEG-PCCL的有效合成，元素分析法以及PEG-PCCL氮芥衍生物双载药胶束的粒径电位考察表明脱盐氮芥和氮芥前药顺利载药，稳定性考察表明PEG-PCCL氮芥衍生物双载药胶束在室温和4℃条件下都具有较好的粒径稳定性。MTT结果表明氮芥脱盐前后治疗效果稳定，一定范围内，相关总药物浓度一致条件下，PEG-PCCL氮芥衍生物双载药胶束的细胞毒性和脱盐氮芥与氮芥前药的比例成正相关。结论：成功制备了氮芥衍生物双载药胶束并进行了相关抗肿瘤研究。 89258

Abstract OBJECTIVE:To improve the safety and efficacy of nitrogen mustard drugs by preparing desulphurized nitrogen mustard and nitrogen mustard produrg double-loaded micelles, and to provide the basis for further study of high-efficiency and low-toxicity nitrogen mustard nano preparations。。 METHODS: A double-loaded micelle was prepared by the method of thin film dispersion using poly (ethylene glycol) -cyclic lactone derivative (PEG-PCCL) as a carrier material for dual-loaded micelles。 The elemental assay Drug content, calculated drug loading。 The size and distribution of particle size and potential were measured by zeta potentiometer。 Stability of PEG-PCCL nitrogen-mustard derivative double-loaded micelles at room temperature and 4 ℃ was investigated。 MTT assay was used to determine the cytotoxicity of K562 cells before and after desalting, and the suitable proportion of desiccated nitrogen mustard and nitrogen mustard was selected to screen PEG-PCCL nitrogen mustard derivatives。Results: 1H-NMR NMR showed that the effective synthesis, elemental analysis and PEG-PCCL nitrogen mustard derivatives were investigated。 The results showed that desalted nitrogen mustard and nitrogen mustard had good drug loading。 The stability of PEG-PCCL nitrogen-mustard derivatives was studied at room temperature and 4 ℃。 The results of MTT showed that the therapeutic effect was stable before and after desulphurization, and the cytotoxicity of PEG-PCCL nitrogen mustard derivative micelles and the ratio of desalted mustard to nitrogen-mustard were within a certain range and consistent with the total drug concentration Related。 Conclusion: Two-loaded micelles of nitrogen mustard derivatives were successfully prepared and related antitumor studies were carried out。

毕业论文关键词：氮芥； 氮芥衍生物； 双载药胶束； 细胞毒性

  Keywords：Nitrogen mustard；Nitrogen mustard derivatives；Drug loaded micelles；Cytotoxicity

目录

1 引言 5

2 实验仪器和试剂 6

3 实验方法 7

3。1体外分析方法的建立 7

3。1。1最大波长来自优Q尔W论E文R网wWw.YouERw.com 加QQ75201.8766 的选择 7

3。1。2氮芥前药标准曲线 7

3。2 PEG-PCCL空白胶束的制备与表征 8

3。2。1 PEG-PCCL的合成