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PEG修饰的大黄酸偶联物的合成及紫杉醇纳米胶束的制备

王夏英, 邱梁桢, 李青卓, 徐伟, 王晓颖

王夏英, 邱梁桢, 李青卓, 徐伟, 王晓颖. PEG修饰的大黄酸偶联物的合成及紫杉醇纳米胶束的制备[J]. 中国药科大学学报, 2018, 49(5): 596-602. DOI: 10.11665/j.issn.1000-5048.20180512
引用本文: 王夏英, 邱梁桢, 李青卓, 徐伟, 王晓颖. PEG修饰的大黄酸偶联物的合成及紫杉醇纳米胶束的制备[J]. 中国药科大学学报, 2018, 49(5): 596-602. DOI: 10.11665/j.issn.1000-5048.20180512
WANG Xiaying, QIU Liangzhen, LI Qingzhuo, XU Wei, WANG Xiaoying. Synthesis of PEGylated carboxymethyl chitosan-rhein conjugate and preparation of paclitaxel-loaded polymeric micelles[J]. Journal of China Pharmaceutical University, 2018, 49(5): 596-602. DOI: 10.11665/j.issn.1000-5048.20180512
Citation: WANG Xiaying, QIU Liangzhen, LI Qingzhuo, XU Wei, WANG Xiaoying. Synthesis of PEGylated carboxymethyl chitosan-rhein conjugate and preparation of paclitaxel-loaded polymeric micelles[J]. Journal of China Pharmaceutical University, 2018, 49(5): 596-602. DOI: 10.11665/j.issn.1000-5048.20180512

PEG修饰的大黄酸偶联物的合成及紫杉醇纳米胶束的制备

基金项目: 国家自然科学基金资助项目(No.81603301);福建省科技厅资助项目(No.2015Y0064);福建省卫计委中青年骨干人才培养资助项目(No.2016-ZQN-69);福建省高校新世纪优秀人才支持计划资助项目(闽教科[2016]No.23)

Synthesis of PEGylated carboxymethyl chitosan-rhein conjugate and preparation of paclitaxel-loaded polymeric micelles

  • 摘要: 抗肿瘤药物紫杉醇(PTX)在水中的溶解度低,其临床制剂Taxol®;所使用的增溶剂Cremophor EL毒副作用大,影响其临床治疗效果。本研究设计PEG修饰羧甲基壳聚糖并接枝大黄酸,合成了两亲性mPEG-羧甲基壳聚糖-大黄酸(CRmP)偶联物,作为PTX的递送载体材料,并制备了载PTX的CRmP纳米胶束(PTX/CRmP纳米胶束)。利用红外光谱(FT-IR)和核磁共振氢谱(1H NMR)对CRmP偶联物进行结构表征。通过动态激光粒径仪(DLS)和原子力显微镜(AFM)对PTX/CRmP纳米胶束的粒径与形态进行表征。通过MTT法评估CRmP偶联物和PTX/CRmP纳米胶束对MCF-7细胞的细胞毒性,结果显示,CRmP偶联物具有良好的安全性;随给药时间的延长,PTX/CRmP纳米胶束在相同药物浓度下表现出优于Taxol®;的体外抗肿瘤活性。
    Abstract: Paclitaxel(PTX), an effective anti-tumor drugs, is water-insoluble. And Cremophor as a solubilizer in its commercial formulation, Taxol® , often causes side-effects which limit its antitumor effect. We designed and synthesized PEGylated carboxymethyl chitosan-rhein(CRmP)conjugate, and further prepared PTX-loaded CRmP polymeric micelles(PTX/CRmP). CRmP conjugate was characterized by fourier transform infrared spectrum(FT-IR)and nuclear magnetic resonance spectroscopy(1H NMR). The particle size and surface morphology of PTX/CRmP were characterized by dynamic laser particle size analyzer(DLS)and atomic force microscope(AFM), respectively. The cytotoxicity of CRmP conjugate and PTX/CRmP against MCF-7 cells were evaluated by MTT assay. The results showed that CRmP conjugates displayed very low cytotoxicity and that PTX/CRmP exhibited better in vitro anti-tumor activity than Taxol® at the same drug concentration after a long-term administration.
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  • 刊出日期:  2018-10-24

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