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采用不同检测方法研究阿霉素结合聚氰基丙烯酸丁酯纳米粒对大鼠胶质瘤细胞系的细胞毒性。

Cytotoxicity of doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles in rat glioma cell lines using different assays.

作者信息

De Juan Berta Sanchez, Von Briesen Hagen, Gelperina Svetlana E, Kreuter Jörg

机构信息

Institute of Pharmaceutical Technology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.

出版信息

J Drug Target. 2006 Nov;14(9):614-22. doi: 10.1080/10611860600866872.

Abstract

The cytotoxicity of doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles (Dox-PBCA-NP) was investigated in the rat glioma cell lines GS-9L, F-98 and RG-2. MTT and LDH assays were used as cytotoxic assays. In general, the cytotoxicity of nanoparticle-bound doxorubicin (Dox) was enhanced compared to the free drug in solution. However, responses of the cell lines towards the drug effects were different. In the case of free Dox in solution, this difference correlated with different intracellular concentrations of Dox, which in turn, depended on the level of P-glycoprotein (P-gp) expression in these cell lines. Accordingly, the 9L gliosarcoma (GS-9L) cells, which appeared to be most resistant towards Dox, were characterized by the highest P-gp expression.Additionally, the influence of surfactants on the cytotoxic effect was investigated at different Dox concentrations. It was shown that the presence of polysorbate 80 (Tween 80) in the nanoparticle formulation significantly enhanced the cytotoxicity, whereas poloxamer 188 (Pluronic F68) and poloxamine 908 (Tetronic 908) had a negligible influence.

摘要

研究了多柔比星结合聚氰基丙烯酸丁酯纳米粒(Dox-PBCA-NP)对大鼠胶质瘤细胞系GS-9L、F-98和RG-2的细胞毒性。采用MTT和LDH法进行细胞毒性检测。总体而言,与溶液中的游离药物相比,纳米粒结合的多柔比星(Dox)的细胞毒性增强。然而,细胞系对药物作用的反应有所不同。对于溶液中的游离Dox,这种差异与不同的细胞内Dox浓度相关,而这又取决于这些细胞系中P-糖蛋白(P-gp)的表达水平。因此,对Dox似乎最具抗性的9L胶质肉瘤(GS-9L)细胞,其P-gp表达水平最高。此外,还研究了表面活性剂在不同Dox浓度下对细胞毒性作用的影响。结果表明,纳米粒制剂中聚山梨酯80(吐温80)的存在显著增强了细胞毒性,而泊洛沙姆188(普朗尼克F68)和泊洛胺908(泰特朗尼克908)的影响可忽略不计。

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