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具有肿瘤靶向及穿膜效应的壳聚糖胶束的制备

Preparation of tumor-targeting chitosan micelle with transmembrane effect

  • 摘要: 在壳聚糖(CS)表面修饰疏水基团辛基形成辛基壳聚糖(OC),然后再修饰亲水基团聚乙二醇(PEG)、肿瘤靶向配体氨基葡萄糖(DG)和穿膜肽九聚精氨酸(9R),形成DG和9R共同修饰的、同时具有肿瘤靶向性及穿膜效应的壳聚糖纳米胶束(DG/9R-PEG-OC)。核磁共振光谱分析及聚丙烯酰胺凝胶电泳检测结果证实了DG/9R-PEG-OC的成功制备;测得壳聚糖纳米胶束的粒径为151.8 nm左右、Zeta电位约为16.5 mV;透射电子显微镜照片显示该壳聚糖纳米胶束为均匀的球形结构;紫外分光光度法测定该载体的荧光素载药量约为28.2%,包封率约为75.0%,释药实验表明壳聚糖胶束具有良好的缓释作用;荧光显微镜观察显示,该DG/9R-PEG-OC胶束对肿瘤细胞尤其是葡萄糖受体高表达的肿瘤细胞HepG2具有较好的靶向性及细胞穿膜效应。故DG/9R-PEG-OC胶束可作为脂溶性抗肿瘤药物的载体用于肿瘤的靶向化学治疗。

     

    Abstract: Chitosan(CS)surface was modified with hydrophobic octyl groups to prepare N-octyl chitosan(nitrogen-octyl chitosan, OC). Then hydrophilic group carboxyl-polyethylene glycol-amino(PEG), tumor-targeting ligand D-glucosamine(DG), and membrane-penetrating peptide 9-D-arginine(9R)were linked to OC successively. Then the DG and 9R modified chitosan micelle(DG/9R-PEG-OC)with tumor-targeting and transmembrane effect was prepared. By hydrogen nuclear magnetic resonance spectrometer(1H NMR)and sodium dodecyl sulfate polyacryl amide gel electrophoresis(SDS-PAGE), the successful formation of DG/9R-PEG-OC was certified, with particle size of 151. 8 nm and Zeta potential of 16. 5 mV. The morphology of chitosan micelle observed by transmission electron microscope was homogeneous spherical structure. The drug loading content(DLC)(using fluorescein as a model drug)and encapsulation efficiency(EE)were about 28. 2% and 75. 0% measured by UV-visible spectrophotometer. Meanwhile, the drug showed a controlled releasing profile out of the micelle. Cellular uptake experiments indicated DG/9R-PEG-OC micelle had a significant tumor-tageting and transmembrane effects, especially on HepG2 cells, which exbihited high expression of the glucose transporter. Thus DG/9R-PEG-OC micelle could be a promising drug targeted delivery system of hydrophobic antitumor drugs.

     

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