Synthesis, in vitro and in vivo evaluation of new norcantharidin-conjugated hydroxypropyltrimethyl ammonium chloride chitosan derivatives as polymer therapeutics

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• 作者：Xiaofen Xu ; Yanggong Li ; Feihu Wang ; Li Lv ; Jieying Liu ; Mingna Li ; Aijie Guo ; Jinjun Jiang ; Yuanyuan Shen ; Shengrong Guo
• 关键词：NCTD-HACC ; Cytotoxicity ; Cellular uptake ; In vivo anti-tumor activity
• 刊名：International Journal of Pharmaceutics
• 出版年：2013
• 出版时间：10 September, 2013
• 年：2013
• 卷：453
• 期：2
• 页码：610-619
• 全文大小：1955 K

文摘

New norcantharidin-conjugated hydroxypropyltrimethyl ammonium chloride chitosan derivatives (NCTD-HACCs) were synthesized and characterized by ¹H NMR, Fourier-transform infrared spectroscopy (FT-IR), and wide-angle X-ray diffraction (WAXD). Two NCTD-HACCs with different degrees of substitution (DS) (12.2 % and 24.8 % ) were obtained, which had good water solubility. NCTD was released from the NCTD-HACCs via hydrolysis, faster in pH 5.0 than pH 7.4 and presenting one biphasic drug release pattern with rapid release at the initial stage and slow release later. Fluorescence microscope and flow cytometry analysis demonstrated that the NCTD-HACC was endocytosized into MGC80-3 cells and the uptaken amount increased as incubation time. Compared with free NCTD, the NCTD-HACCs showed lower in vitro anti-tumor activity against human gastric cancer MGC80-3 cells, but higher in vivo tumor growth inhibition in S180 tumor-bearing mice. The in vivo near-infrared (NIR) fluorescence real-time imaging result showed the fluorescence intensity in tumor was much higher than that in heart, liver, spleen and lung (except kidney) after i.v. injection of the FITC-labeled NCTD-HACC2, indicating specific accumulation of the NCTD-HACC in tumor.