替尼泊苷多层包衣白蛋白纳米粒的制备工艺及体外抗肿瘤活性

发布时间：2018-03-11 06:17

本文选题：替尼泊苷　切入点：多层包衣白蛋白纳米粒　出处：《沈阳药科大学学报》2017年09期 　论文类型：期刊论文

【摘要】：目的以人血清白蛋白为载体包载替尼泊苷,经过包衣修饰后制备包载替尼泊苷的多层包衣纳米粒(teniposide-encapsulated multilayer nanoparticles,P-CS-NP),以期降低药物的不良反应并改善其体外抗肿瘤活性。方法以粒径、多分散指数和载药率为评价指标,采用单一因素法筛选出替尼泊苷白蛋白纳米粒的最优处方工艺,通过加入壳聚糖和聚谷氨酸聚乙二醇共聚物进一步制备多层包衣白蛋白纳米粒,筛选得到最优包衣量。以游离的替尼泊苷作为参比,用MTT法测定纳米粒对人肺癌A549细胞的体外细胞毒性,并用流式细胞仪和共聚焦显微镜测定和观察多层包衣纳米粒的细胞摄取率和细胞摄取行为。结果确定了多层包衣纳米粒的处方及制备工艺。多层包衣纳米粒的体外细胞毒性比游离的替尼泊苷小,摄取具有时间依赖性,与壳聚糖共孵育的纳米粒的细胞摄取量增加,入胞后纳米粒主要分布在细胞质。结论白蛋白纳米粒能被壳聚糖和聚谷氨酸聚乙二醇共聚物包衣修饰,多层包衣纳米粒可以作为替尼泊苷的药物递送载体,其体外细胞毒性降低。
[Abstract]:Objective to prepare teniposide-coated multilayer nanoparticles-P-CS-NPP coated with human serum albumin (HSA) as carrier and coated with teniposide-apsulated nanoparticles-P-CS-NPP, in order to reduce adverse drug reactions and improve its antitumor activity in vitro. The polydispersity index and drug loading rate were used as the evaluation indexes. The optimal formulation process of teniposide albumin nanoparticles was selected by single factor method. The multilayer coated albumin nanoparticles were prepared by adding chitosan and poly (ethylene glycol glutamate) copolymers, and the optimal coating amount was obtained. The free teniposide was used as the reference. The cytotoxicity of nanoparticles to human lung cancer A549 cells in vitro was determined by MTT assay. The cell uptake rate and cell uptake behavior of multilayer coated nanoparticles were measured and observed by flow cytometry and confocal microscopy. The formulation and preparation process of multilayer coated nanoparticles were determined. The extracellular toxicity was less than that of free teniposide. The uptake was time-dependent, and the uptake of the nanoparticles incubated with chitosan increased, and the nanoparticles mainly distributed in the cytoplasm. Conclusion Albumin nanoparticles can be coated with chitosan and poly (glutamic acid) polyethylene glycol copolymers. Multilayer coated nanoparticles can be used as drug delivery carriers of teniposide, and their cytotoxicity is decreased in vitro.
【作者单位】：沈阳药科大学药学院;
【分类号】：R943;R96

【相似文献】