Department of Pharmaceutics, School of Pharmacy, Soochow University, Suzhou, China.
Nanomedicine. 2010 Apr;6(2):371-81. doi: 10.1016/j.nano.2009.07.006. Epub 2009 Aug 20.
In this study a new chitosan (CS) derivative, galactosylated chitosan (GC), was synthesized and used to prepare norcantharidin-associated GC nanoparticles (NCTD-GC NPs) by taking advantage of the ionic cross-linkage between the molecules of the anti-hepatocarcinoma medicine NCTD and of the GC as carrier. NCTD-GC NPs were obtained with average particle size of 118.68 +/- 3.37 nm, entrapment efficiency of 57.92 +/- 0.40%, and drug-loading amount of 10.38 +/- 0.06%. Several important factors influencing the entrapment efficiency, drug-loading amount, and particle size of NCTD-GC NPs were studied. The characteristics of sustained and pH-sensitive release of NCTD from NCTD-GC NPs in vitro were studied. In addition, in vitro cellular uptake and cytotoxicity of nanoparticles to hepatoma cell lines SMMC-7721 and HepG2 were also investigated. In vitro, and compared to CS-based NCTD-CS NPs, NCTD-GC NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against hepatocellular carcinoma cells. In vivo antitumor activity of NCTD-GC NPs was evaluated in mice bearing H22 liver tumors. NCTD-GC NPs displayed tumor inhibition effect in mice, better than either the free NCTD or the NCTD-CS NPs. As a hepatocyte-targeting carrier, GC NPs are potentially promising for clinical applications.
In this paper, a galactosylated chitosan (GC), was synthesized and norcantharidin (NCTD)-associated galactosylated chitosan nanoparticles (NCTDGC NPs) were generated by coupling NCTD--an anti-hepatocarcinoma drug--and GC as carrier. Compared to chitosan nanoparticles, NCTD-GC-NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against the cells.
在这项研究中，合成了一种新的壳聚糖（CS）衍生物——半乳糖化壳聚糖（GC），并利用抗肝癌药物去甲斑蝥素（NCTD）分子与 GC 作为载体之间的离子交联作用，制备了 NCTD-GC 纳米颗粒（NCTD-GC NPs）。NCTD-GC NPs 的平均粒径为 118.68 ± 3.37nm，包封率为 57.92 ± 0.40%，载药量为 10.38 ± 0.06%。研究了影响 NCTD-GC NPs 包封率、载药量和粒径的几个重要因素。研究了 NCTD-GC NPs 在体外的持续和 pH 敏感释放特性。此外，还研究了纳米颗粒对肝癌细胞系 SMMC-7721 和 HepG2 的体外细胞摄取和细胞毒性。体外研究结果表明，与基于 CS 的 NCTD-CS NPs 相比，NCTD-GC NPs 与肝癌细胞具有良好的相容性，对肝癌细胞具有较强的细胞毒性。在荷 H22 肝癌小鼠体内评价了 NCTD-GC NPs 的抗肿瘤活性。NCTD-GC NPs 在小鼠体内显示出肿瘤抑制作用，优于游离 NCTD 或 NCTD-CS NPs。作为一种肝细胞靶向载体，GC NPs 在临床上具有应用潜力。
本文合成了一种半乳糖化壳聚糖（GC），并通过将 NCTD——一种抗肝癌药物——与 GC 作为载体偶联，生成了半乳糖化壳聚糖纳米颗粒（NCTD-GC-NPs）。与壳聚糖纳米颗粒相比，NCTD-GC-NPs 与肝癌细胞具有良好的相容性，对肝癌细胞具有较强的细胞毒性。
