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Cytotoxicity of doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles in rat glioma cell lines using different assays
Authors:Berta Sanchez De Juan  Hagen Von Briesen  Svetlana E Gelperina  Jörg Kreuter
Affiliation:1. Institute of Pharmaceutical Technology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany;2. Fraunhofer Institute for Biomedical Engineering, St. Ingbert, Germany;3. Center of Molecular Diagnostics and Therapy, Moscow, Russia
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.
Keywords:Cytotoxicity  doxorubicin  poly (butyl cyanoacrylate) nanoparticles  rat glioma cell lines  surfactants
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