基于壳聚糖中空纳米球的紫杉醇给药系统对肺癌细胞A549的作用研究
发布时间：2019-06-30 21:02
【摘要】：目的制备一种基于生物可降解壳聚糖中空纳米球的紫杉醇纳米给药系统,旨在改善难溶性药物的水溶性、调节药物释放,增加其疗效。以人肺癌细胞A549为模型,研究壳聚糖中空纳米球(CHN)载药后促进药物吸收作用,为肺癌治疗提供支持。方法本研究以抗癌药物紫杉醇(PTX)为模型药物,通过吸附平衡法将PTX吸附到CHN的中空结构中。通过透射电子显微镜(TEM)和扫描电子显微镜(SEM)研究CHN的形态结构。通过差示扫描量热法(DSC),粉末X射线衍射法(PXRD)和傅里叶红外光谱法(FTIR)对PTX进行固体状态的表征。通过体外释放度实验研究紫杉醇的释放行为。通过细胞毒性试验和细胞摄取实验探究了壳聚糖中空纳米球的紫杉醇纳米给药系统对肺癌细胞A549的影响。进行了载药样品(PTX-CHN)在家兔体内的药代动力学实验。结果本研究成功制备了生物可降解壳聚糖中空纳米球。在PTX-CHN药物释放中,PTX呈缓释释放。通过DSC、PXRD和FTIR对PTX在载体中的固体状态进行表征,结果表明PTX在CHN中以非晶型状态存在。体外毒性试验表明CHN具有良好的生物安全性。PTX-CHN能够显著抑制肺癌细胞A549的增殖并促进其凋亡。细胞摄取实验表明PTX-CHN能够被肺癌细胞A549摄取。降解实验表明CHN是生物可降解的。体内药代动力学实验结果表明PTX-CHN能够提高紫杉醇在家兔体内的疗效。结论CHN能够提高水难溶性药物PTX的水溶性,调节药物释放速率,提高疗效,CHN作为一种生物可降解的生物材料,能够被肺癌细胞A549摄取,促进药物吸收,在肺癌治疗中具有良好的应用前景。
[Abstract]:Objective to prepare a paclitaxel nano-drug delivery system based on biodegradable chitosan hollow nanosphere in order to improve the water solubility of insoluble drugs, regulate drug release and increase its curative effect. Human lung cancer cell line A549 was used as a model to study the effect of chitosan hollow nanosphere (CHN) on promoting drug absorption and providing support for the treatment of lung cancer. Methods the anticancer drug paclitaxel (PTX) was used as the model drug to adsorb PTX into the hollow structure of CHN by adsorption equilibrium method. The morphology and structure of CHN were studied by transmission electron microscope (TEM) and scanning electron microscope (SEM). The solid state of PTX was characterized by differential scanning Calorimeter (DSC),) powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). The release behavior of paclitaxel was studied by in vitro release test. The effect of paclitaxel nano-delivery system on lung cancer cell line A549 was studied by cytotoxicity test and cell uptake test. The pharmacokinetics of drug-loaded samples (PTX-CHN) in rabbits was studied. Results Biodegradable chitosan hollow nanoparticles were successfully prepared. In the drug release of PTX-CHN, PTX was released slowly. The solid state of PTX in the carrier was characterized by DSC,PXRD and FTIR. The results showed that PTX existed in amorphous state in CHN. In vitro toxicity test showed that CHN had good biosafety. PTX-CHN could significantly inhibit the proliferation and promote apoptosis of lung cancer cell line A549. Cell uptake assay showed that PTX-CHN could be ingested by lung cancer cell line A549. The degradation experiment showed that CHN was biodegradable. The results of pharmacokinetics in vivo showed that PTX-CHN could improve the efficacy of paclitaxel in rabbits. Conclusion CHN can improve the water solubility of water insoluble drug PTX, regulate the drug release rate and improve the curative effect. CHN, as a biodegradable biomaterial, can be ingested by lung cancer cell line A549 and promote drug absorption. CHN has a good application prospect in the treatment of lung cancer.
【学位授予单位】：锦州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943;R96
[Abstract]:Objective to prepare a paclitaxel nano-drug delivery system based on biodegradable chitosan hollow nanosphere in order to improve the water solubility of insoluble drugs, regulate drug release and increase its curative effect. Human lung cancer cell line A549 was used as a model to study the effect of chitosan hollow nanosphere (CHN) on promoting drug absorption and providing support for the treatment of lung cancer. Methods the anticancer drug paclitaxel (PTX) was used as the model drug to adsorb PTX into the hollow structure of CHN by adsorption equilibrium method. The morphology and structure of CHN were studied by transmission electron microscope (TEM) and scanning electron microscope (SEM). The solid state of PTX was characterized by differential scanning Calorimeter (DSC),) powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). The release behavior of paclitaxel was studied by in vitro release test. The effect of paclitaxel nano-delivery system on lung cancer cell line A549 was studied by cytotoxicity test and cell uptake test. The pharmacokinetics of drug-loaded samples (PTX-CHN) in rabbits was studied. Results Biodegradable chitosan hollow nanoparticles were successfully prepared. In the drug release of PTX-CHN, PTX was released slowly. The solid state of PTX in the carrier was characterized by DSC,PXRD and FTIR. The results showed that PTX existed in amorphous state in CHN. In vitro toxicity test showed that CHN had good biosafety. PTX-CHN could significantly inhibit the proliferation and promote apoptosis of lung cancer cell line A549. Cell uptake assay showed that PTX-CHN could be ingested by lung cancer cell line A549. The degradation experiment showed that CHN was biodegradable. The results of pharmacokinetics in vivo showed that PTX-CHN could improve the efficacy of paclitaxel in rabbits. Conclusion CHN can improve the water solubility of water insoluble drug PTX, regulate the drug release rate and improve the curative effect. CHN, as a biodegradable biomaterial, can be ingested by lung cancer cell line A549 and promote drug absorption. CHN has a good application prospect in the treatment of lung cancer.
【学位授予单位】：锦州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943;R96
【相似文献】
相关期刊论文 前8条
1 余欣尉;吴谦;吕望;王彦;马小琼;陈U，
本文编号：2508248
本文链接：https://www.wllwen.com/yixuelunwen/yiyaoxuelunwen/2508248.html
最近更新
教材专著
