基于磷脂包裹介孔中空二氧化硅纳米球的阿霉素—紫杉醇联合给药体系对肺癌细胞A549的作用研究

发布时间：2018-06-25 11:59

本文选题：磷脂包裹介孔中空二氧化硅纳米球 + 紫杉醇　；参考：《锦州医科大学》2017年硕士论文

【摘要】：目的本实验制备磷脂包裹介孔中空二氧化硅纳米球(L-HMSN),以其为载体,同时包载紫杉醇和阿霉素,研究该载药体系对A549细胞的作用机制。方法通过模板法制备介孔中空二氧化硅纳米球,进一步采用薄膜水化法将磷脂包裹在球表面以获得载体L-HMSN。以阿霉素和紫杉醇作为模型药物,阿霉素通过吸附法被吸附到L-HMSN的中空结构里,而紫杉醇随磷脂通过薄膜水化法被包裹在介孔中空二氧化硅纳米粒表面,最终制备成载药体系(DOX/PTX@L-HMSN)。采用透射电镜(TEM)、差示扫描量热法(DSC)、X射线衍射法(XRPD)和傅里叶红外光谱(FT-IR)等手段对载药体系进行表征。通过细胞实验对L-HMSN进行生物安全性评价,并研究载药系统对肺癌细胞A549的作用。通过体外释放实验考察载体对两种药物释放速率的影响,并进行家兔体内药代动力学研究。结果表征结果表明阿霉素和紫杉醇是以无定型的状态存在于纳米球中。体外释放实验结果表明载药体系中两种药物实现缓释释放。细胞摄取实验证明L-HMSN成功地被摄取到A549细胞中。此外,载药体系中阿霉素和紫杉醇的联合使用在抑制A549细胞增长中展现了显著的协同效应。体内药代动力学研究结果表明L-HMSN实现了阿霉素和紫杉醇的联合应用,且提高了药物疗效。结论研究结果表明L-HMSN不仅能避免两药的相互作用,实现两药的联合使用,而且能够调节药物释放,提高药物疗效。此外,L-HMSN具有高比表面积,大的孔容积,可调节药物释放速率的介孔壳结构,表面易改性等优点,是一种良好的药物载体。因此,L-HMSN作为两种药物的载体在联合给药系统中具有很大的发展前景。
[Abstract]:Objective to prepare phospholipid encapsulated mesoporous silica nanospheres (L-HMSN), and to study the mechanism of the drug delivery system on A549 cells by encapsulating paclitaxel and doxorubicin. Methods the mesoporous hollow silica nanospheres were prepared by template method. The phospholipids were encapsulated on the surface of the spheres by membrane hydration to obtain the carrier L-HMSN. Using adriamycin and paclitaxel as model drugs, doxorubicin was adsorbed into the hollow structure of L-HMSN by adsorption, while paclitaxel was encapsulated on the surface of mesoporous hollow silica nanoparticles by membrane hydration of phospholipid. The system was characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRPD) and Fourier transform infrared spectroscopy (FT-IR). The biological safety of L-HMSN was evaluated by cell experiment and the effect of drug delivery system on lung cancer cell line A549 was studied. The effect of carrier on the release rate of two drugs was investigated in vitro, and the pharmacokinetics of the two drugs was studied in vivo. The results showed that adriamycin and paclitaxel existed in the nanospheres in an amorphous state. The results of in vitro release test showed that two drugs in the drug delivery system could be released sustainably. In addition, the combination of adriamycin and paclitaxel in the drug delivery system showed a significant synergistic effect in inhibiting the growth of A549 cells. The results of in vivo pharmacokinetic study showed that L-HMSN combined with adriamycin and paclitaxel and improved the therapeutic effect. Conclusion L-HMSN can not only avoid the interaction between the two drugs, but also regulate the drug release and improve the efficacy of the two drugs. In addition, L-HMSN has the advantages of high specific surface area, large pore volume, mesoporous shell structure with adjustable drug release rate and easy surface modification, so it is a good drug carrier. Therefore, L-HMSN as a carrier of two drugs in the combined drug delivery system has a great development prospects.
【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

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