%0 Journal Article %1 fischer2003vitro %A Fischer, Dagmar %A Li, Youxin %A Ahlemeyer, Barbara %A Krieglstein, Josef %A Kissel, Thomas %D 2003 %J Biomaterials %K cytotox nextgen polymer %N 7 %P 1121--1131 %R http://dx.doi.org/10.1016/S0142-9612(02)00445-3 %T In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis %U http://www.sciencedirect.com/science/article/pii/S0142961202004453 %V 24 %X A comparative in vitro cytotoxicity study with different water-soluble, cationic macromolecules which have been described as gene delivery systems was performed. Cytotoxicity in Ł929\ mouse fibroblasts was monitored using the \MTT\ assay and the release of the cytosolic enzyme lactate dehydrogenase (LDH). Microscopic observations were carried out as indicators for cell viability. Furthermore, hemolysis of erythrocytes was quantified spectrophotometrically. To determine the nature of cell death induced by the polycations, the nuclear morphology after \DAPI\ staining and the inhibition of the toxic effects by the caspase inhibitor zVAD.fmk were investigated. All assays yielded comparable results and allowed the following ranking of the polymers with regard to cytotoxicity: Poly(ethylenimine)=poly(l-lysine)>poly(diallyl-dimethyl-ammonium chloride)>diethylaminoethyl-dextran>poly(vinyl pyridinium bromide)>Starburst dendrimer>cationized albumin>native albumin. The magnitude of the cytotoxic effects of all polymers were found to be time- and concentration dependent. The molecular weight as well as the cationic charge density of the polycations were confirmed as key parameters for the interaction with the cell membranes and consequently, the cell damage. Evaluating the nature of cell death induced by poly(ethylenimine), we did not detect any indication for apoptosis suggesting that the polymer induced a necrotic cell reaction. Cell nuclei retained their size, chromatin was homogenously distributed and cell membranes lost their integrity very rapidly at an early stage. Furthermore, the broad spectrum caspase inhibitor zVAD.fmk did not inhibit poly(ethylenimine)-induced cell damage. Insights into the structure–toxicity relationship are necessary to optimize the cytotoxicity and biocompatibility of non-viral gene delivery systems.

@article{fischer2003vitro, abstract = {A comparative in vitro cytotoxicity study with different water-soluble, cationic macromolecules which have been described as gene delivery systems was performed. Cytotoxicity in \{L929\} mouse fibroblasts was monitored using the \{MTT\} assay and the release of the cytosolic enzyme lactate dehydrogenase (LDH). Microscopic observations were carried out as indicators for cell viability. Furthermore, hemolysis of erythrocytes was quantified spectrophotometrically. To determine the nature of cell death induced by the polycations, the nuclear morphology after \{DAPI\} staining and the inhibition of the toxic effects by the caspase inhibitor zVAD.fmk were investigated. All assays yielded comparable results and allowed the following ranking of the polymers with regard to cytotoxicity: Poly(ethylenimine)=poly(l-lysine)>poly(diallyl-dimethyl-ammonium chloride)>diethylaminoethyl-dextran>poly(vinyl pyridinium bromide)>Starburst dendrimer>cationized albumin>native albumin. The magnitude of the cytotoxic effects of all polymers were found to be time- and concentration dependent. The molecular weight as well as the cationic charge density of the polycations were confirmed as key parameters for the interaction with the cell membranes and consequently, the cell damage. Evaluating the nature of cell death induced by poly(ethylenimine), we did not detect any indication for apoptosis suggesting that the polymer induced a necrotic cell reaction. Cell nuclei retained their size, chromatin was homogenously distributed and cell membranes lost their integrity very rapidly at an early stage. Furthermore, the broad spectrum caspase inhibitor zVAD.fmk did not inhibit poly(ethylenimine)-induced cell damage. Insights into the structure–toxicity relationship are necessary to optimize the cytotoxicity and biocompatibility of non-viral gene delivery systems. }, added-at = {2016-11-02T11:18:03.000+0100}, author = {Fischer, Dagmar and Li, Youxin and Ahlemeyer, Barbara and Krieglstein, Josef and Kissel, Thomas}, biburl = {https://www.bibsonomy.org/bibtex/223fb67e0155944e8918356009e9fec58/bkoch}, description = {In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis}, doi = {http://dx.doi.org/10.1016/S0142-9612(02)00445-3}, interhash = {d7318f6cf3d8787e61797e984dac4a2f}, intrahash = {23fb67e0155944e8918356009e9fec58}, issn = {0142-9612}, journal = {Biomaterials }, keywords = {cytotox nextgen polymer}, number = 7, pages = {1121--1131}, timestamp = {2016-11-02T11:18:03.000+0100}, title = {In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis }, url = {http://www.sciencedirect.com/science/article/pii/S0142961202004453}, volume = 24, year = 2003 }