PEG修饰的大黄酸偶联物的合成及紫杉醇纳米胶束的制备

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

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m PEG-羧甲基壳聚糖-大黄酸(CRm P)偶联物,作为PTX的递送载体材料,并制备了载PTX的CRm P纳米胶束(PTX/CRm P纳米胶束)。利用红外光谱(FT-IR)和核磁共振氢谱(~1H NMR)对CRm P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/CRm P纳米胶束的粒径与形态进行表征。通过MTT法评估CRm P偶联物和PTX/CRm P纳米胶束对MCF-7细胞的细胞毒性,结果显示,CRm P偶联物具有良好的安全性;随给药时间的延长,PTX/CRm P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。

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(1 H 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.