5-FU负载聚乳酸-羟基乙酸纳米颗粒治疗肺癌的研究进展

Sankha Bhattacharya
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引用次数: 3

摘要

迄今为止,非小细胞肺癌(NSCLC)约占所有肺癌类型的84%。每年,不分性别,NSCLC的目标是全世界的许多社区。5-氟尿嘧啶(5-FU)是一种类似于尿嘧啶的抗癌化合物。这种药能消灭多个肿瘤细胞。但5-FU最大的障碍是它很容易在血液中代谢,最终导致抗癌活性降低。因此,需要一个完善的给药系统来克服所有相关的挑战。本实验尝试采用溶剂蒸发法制备负载5-FU的聚乳酸-共乙醇酸纳米颗粒,并观察了负载5-FU的聚乳酸-共乙醇酸分子量、负载量、超声时间对10% w/w负载5-FU的PLGA纳米颗粒对人A549等基因细胞株的细胞毒作用的影响。在本实验中,有两点更为明显:第一,聚乳酸-羟基乙酸在纳米颗粒溶液中具有较高的降解和扩散速率,对5-FU的释放有重要影响;其次,表面积越大、粒径越小的纳米颗粒,其半最大抑制浓度(IC50)值越低。各纳米颗粒的IC50均显著高于游离5-FU对照组(8.34Nm) (p=0.0145)。IC50值越低,细胞毒性越大。超声时间为18分钟的纳米颗粒比含有12%聚乙烯醇的PLGA纳米颗粒具有更大的细胞毒性。本实验制备了10% w/w 5-FU负载的聚乳酸-羟基乙酸纳米颗粒,用于实验室研究到肺癌治疗的转化研究。
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Development of 5-FU Loaded poly lactic-co-glycolic acid Nanoparticles for Treatment of Lung Cancer
Non-Small Cell Lung Cancer (NSCLC) accounts for about 84% of all lung cancer types diagnosed so far. Every year, regardless of gender, the NSCLC targets many communities worldwide. 5-Fluorouracil (5-FU) is a uracil-analog anticancer compound. This drug tends to annihilate multiple tumour cells. But 5-FU's most significant obstacle is that it gets very easily metabolized in the blood, which eventually leads to lower anticancer activity. Therfore a perfect drug delivery system is needed to overcome all the associated challenges. In this experiment, an attempt was made to prepare 5-FU loaded poly lactic-co-glycolic acid  nanoparticles using solvent evaporation method and subsequently observed the effect of molecular weight of poly lactic-co-glycolic acid, loading of poly lactic-co-glycolic acid, sonication period on the cytotoxic effect of 10 % w/w 5-FU loaded PLGA nanoparticles against human A549 Isogenic cell line. In this experiment, two points are more evident: first, poly lactic-co-glycolic acid has a major impact on 5-FU release due to higher degradation and rate of diffusion in nanoparticle solution; and second, nanoparticles with a larger surface area and smaller particle size have a lower half-maximal inhibitory concentration (IC50) value. The IC50 of all nanoparticles was significantly higher (p=0.0145) than that of the free 5-FU controlled group (8.34Nm). The cytotoxicity would be greater if the IC50 value was lower. Nanoparticles with an 18-minute sonication time was found to  be more cytotoxic than those with PLGA nanoparticles containing 12% polyvinyl alcohol.  In this experiment 10% w/w 5-FU loaded poly lactic-co-glycolic acid nanoparticles was prepared for laboratory research to translational research for the treatment of lung cancer.
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