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首页> 美国卫生研究院文献>International Journal of Nanomedicine >Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics
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Optimized synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and their characteristics

机译：甘草次酸修饰的壳聚糖5-氟尿嘧啶纳米粒子的优化合成及其性质

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The nanoparticle drug delivery system, which uses natural or synthetic polymeric material as a carrier to deliver drugs to targeted tissues, has a broad prospect for clinical application for its targeting, slow-release, and biodegradable properties. Here, we used chitosan (CTS) and hepatoma cell-specific binding molecule glycyrrhetinic acid to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared (IR) spectra and hydrogen-1 nuclear magnetic resonance. The GA-CTS/5-fluorouracil (5-FU) nanoparticles were synthesized by combining GA-CTS and 5-FU and conjugating 5-FU onto the GA-CTS nanomaterial. The central composite design was performed to optimize the preparation process as CTS:tripolyphosphate sodium (TPP) weight ratio =5:1, 5-FU:CTS weight ratio =1:1, TPP concentration =0.05% (w/v), and cross-link time =50 minutes. GA-CTS/5-FU nanoparticles had a mean particle size of 193.7 nm, a polydispersity index of 0.003, a zeta potential of +27.4 mV, and a drug loading of 1.56%. The GA-CTS/5-FU nanoparticle had a protective effect on the drug against plasma degrading enzyme, and provided a sustained release system comprising three distinct phases of quick, steady, and slow release. Our study showed that the peak time, half-life time, mean residence time and area under the curve of GA-CTS/5-FU were longer or more than those of the 5-FU group, but the maximum concentration (Cmax) was lower. We demonstrated that the nanoparticles accumulated in the liver and have significantly inhibited tumor growth in an orthotropic liver cancer mouse model.
机译：使用天然或合成聚合物材料作为载体将药物输送到目标组织的纳米粒子药物输送系统，由于其靶向，缓释和可生物降解的特性，在临床上具有广阔的前景。在这里，我们使用壳聚糖（CTS）和肝癌细胞特异性结合分子甘草次酸合成了甘草次酸修饰的壳聚糖（GA-CTS）。通过红外（IR）光谱和氢-1核磁共振证实了合成产物。 GA-CTS / 5-氟尿嘧啶（5-FU）纳米粒子是通过将GA-CTS和5-FU结合并将5-FU共轭到GA-CTS纳米材料上而合成的。进行中央复合材料设计以优化制备过程，如CTS：三聚磷酸钠（TPP）重量比= 5：1、5-FU：CTS重量比= 1：1，TPP浓度= 0.05％（w / v）和交叉链接时间= 50分钟。 GA-CTS / 5-FU纳米粒子的平均粒径为193.7 nm，多分散指数为0.003，ζ电位为+27.4 mV，载药量为1.56％。 GA-CTS / 5-FU纳米颗粒对药物具有抗血浆降解酶的保护作用，并提供了一个包括三个不同阶段的快速，稳定和缓慢释放的持续释放系统。我们的研究表明，GA-CTS / 5-FU曲线下的峰时间，半衰期，平均停留时间和面积比5-FU组更长或更长，但最大浓度（Cmax）为降低。我们证明了纳米粒子在肝脏中积累，并在正交异性肝癌小鼠模型中显着抑制了肿瘤的生长。

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