Synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and its inhibition of liver cancer characteristics in vitro and in vivo.
Synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and its inhibition of liver cancer characteristics in vitro and in vivo.
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DOI：
10.3390/md11093517
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发表时间：
2013-09-17
期刊：
影响因子：
5.4
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Cheng M;Gao X;Wang Y;Chen H;He B;Xu H;Li Y;Han J;Zhang Z
纳米药物传递系统是一种新型的药物传递系统，药物通过纳米级的小颗粒传递到作用部位。天然或合成聚合物被用作NDDS的载体，因为它们具有靶向性、缓释性和生物降解性。在这里，我们利用壳聚糖和肝癌细胞特异性结合分子甘草次酸(GA)，合成了甘草次酸修饰的壳聚糖(GA-CTS)。合成产物经傅立叶变换红外光谱(FT-IR)和核磁共振氢谱(1H-核磁共振)确证。将GA-CTS与5-FU(5-FU)复合，制得了粒径为217.2 nm、载药量为1.56%、多分散指数为0.003的GA-CTS/5-FU纳米粒。GA-CTS/5-FU纳米粒提供了一个由快速、稳定和缓慢释放三个不同阶段组成的缓释体系。我们证明了纳米颗粒在肝脏中积累。体外实验数据表明，它具有剂量和时间依赖性的抗癌作用。与5-FU相比，药物对肝癌细胞的有效药物暴露时间延长。GA-CTS/5-FU对耐药肝癌的生长有明显的抑制作用，这可能是对5-FU耐药性的补偿。体内实验表明，GA-CTS/5-FU能显著抑制肿瘤生长，延长小鼠生存期。
Nanoparticle drug delivery (NDDS) is a novel system in which the drugs are delivered to the site of action by small particles in the nanometer range. Natural or synthetic polymers are used as vectors in NDDS, as they provide targeted, sustained release and biodegradability. Here, we used the chitosan and hepatoma cell-specific binding molecule, glycyrrhetinic acid (GA), to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by Fourier transformed infrared spectroscopy (FT-IR) and 1H-nuclear magnetic resonance (1H-NMR). By combining GA-CTS and 5-FU (5-fluorouracil), we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 217.2 nm, a drug loading of 1.56% and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained release system comprising three distinct phases of quick, steady and slow release. We demonstrated that the nanoparticle accumulated in the liver. In vitro data indicated that it had a dose- and time-dependent anti-cancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. Additionally, GA-CTS/5-FU significantly inhibited the growth of drug-resistant hepatoma, which may compensate for the drug-resistance of 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited tumor growth, resulting in increased survival time.
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影响因子：
20.3
作者：
Giannì, M;Koken, MHM;de Thé, H
通讯作者：
de Thé, H
DOI：
10.1016/j.ijbiomac.2011.12.034
发表时间：
2012-03-01
影响因子：
8.2
作者：
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影响因子：
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作者：
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DOI：
10.1007/s10856-011-4262-2
发表时间：
2011-04-01
影响因子：
3.7
作者：
Huang, Wei;Wang, Wei;Yuan, Zhi
通讯作者：
Yuan, Zhi
影响因子：
3.7
作者：
Cheng M;He B;Wan T;Zhu W;Han J;Zha B;Chen H;Yang F;Li Q;Wang W;Xu H;Ye T
通讯作者：
Ye T