负载雷替曲塞的HSA纳米微球的生物性能研究

发布时间：2018-05-21 12:27

本文选题：人血清白蛋白 + 雷替曲塞　；参考：《南京大学》2014年硕士论文

【摘要】：为了提高结直肠癌临床用药雷替曲塞(Raltitrexed)的水溶性,延长其血液循环时间,降低毒副作用并提高其被动靶向性能,本工作通过去溶剂法制备了一系列不同粒径和载药量的负载雷替曲塞的人血清白蛋白(Human Serum Albumin, HSA)纳米微球,通过细胞和动物两个层面上研究了载药纳米微球的生物性能。我们通过谷胱甘肽(GSH)还原人血清白蛋白中的二硫键,而后采用去溶剂法合成了负载雷替曲塞的HSA纳米微球,最后通过热固法提高纳米微球的稳定性。考察了纳米微球的粒径、载药效率、包封率以及稳定性；将上述载药纳米微球与细胞共培养,通过MTT法测定了载药纳米微球细胞毒性,通过激光共聚焦显微镜观测其细胞摄取情况；建立了BALB/C小鼠皮下接种CT-26鼠源结肠癌细胞肿瘤模型,通过近红外荧光成像方法跟踪纳米微球在荷瘤小鼠体内实时分布情况,通过HPLC-UV的方法测定雷替曲塞在小鼠体内分布,实验结果均以单独注射等计量雷替曲塞药物作为对照组进行讨论。结果表明：纳米微球的粒径和载药量具有良好的可控性,能够通过胞吞作用进入细胞,实现药物的缓释,并可利用增强的渗透和滞留(EPR)效应在肿瘤组织有效富集。
[Abstract]:In order to improve the water solubility, prolong the blood circulation time, reduce the toxic side effects and improve the passive targeting performance of Raltitrexide, a clinical drug for colorectal cancer, In this work, a series of human serum albumin (Serum Albumin, HSA) loaded with different particle size and drug loading amount were prepared by solvent removal method. The biological properties of the drug loaded nanoparticles were studied at the cell and animal levels. The disulfide bond in human serum albumin was reduced by glutathione (GSH), then the HSA nanospheres loaded with retitrexed were synthesized by solvent removal method. Finally, the stability of the nanoparticles was improved by thermosetting method. The particle size, drug loading efficiency, encapsulation efficiency and stability of the nanoparticles were investigated, and the cytotoxicity of the drug loaded nanoparticles was determined by MTT method. The cell uptake was observed by laser confocal microscope, the tumor model of colon cancer cells from CT-26 mice was established by subcutaneous inoculation of BALB/C mice, and the real-time distribution of nanoparticles in tumor-bearing mice was tracked by near-infrared fluorescence imaging. The distribution of letitrexed in mice was determined by HPLC-UV. The results showed that the particle size and drug loading of the nanoparticles had good controllability and could enter the cells through the cytosolic action to realize the sustained release of the drug, and the enhanced permeation and retention EPR-effect could be used to effectively enrich the tumor tissue.
【学位授予单位】：南京大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

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