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LIU Wanwan, ZHANG Shengyu, YANG Yu, ZHU Hongyan. Preparation of tumor-targeting chitosan micelle with transmembrane effect[J]. Journal of China Pharmaceutical University, 2015, 46(5): 561-567. DOI: 10.11665/j.issn.1000-5048.20150508
Citation: LIU Wanwan, ZHANG Shengyu, YANG Yu, ZHU Hongyan. Preparation of tumor-targeting chitosan micelle with transmembrane effect[J]. Journal of China Pharmaceutical University, 2015, 46(5): 561-567. DOI: 10.11665/j.issn.1000-5048.20150508

Preparation of tumor-targeting chitosan micelle with transmembrane effect

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  • 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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