title: Cytotoxicity of doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles in rat glioma cell lines using different assays.
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.
authors.affiliation: Institute of Pharmaceutical Technology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.
authors.forename: Berta Sanchez
authors.initials: BS
authors.lastname: De Juan
authors.forename: Hagen
authors.initials: H
authors.lastname: Von Briesen
authors.forename: Svetlana E
authors.initials: SE
authors.lastname: Gelperina
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D004317:Doxorubicin / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use*; D004659:Enbucrilate / Q000737:chemistry*; D005079:Excipients; D005434:Flow Cytometry; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018613:Microscopy, Confocal; D053758:Nanoparticles; D051381:Rats; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D005079:Excipients; D013778:Tetrazolium Salts; D013844:Thiazoles; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; D004659:Enbucrilate