Graphene oxide (GO) has been a focus of research in the fields of electronics, energy, and biomedicine, including drug delivery. Thus, single- and multi-layered GO (SLGO and MLGO) have been produced and investigated. However, little information on their toxicity and biocompatibility is available. In the present study, we performed a comprehensive study of the size- and dose-dependent toxicity of GOs in the presence or absence of Pluronic F-127 on THP-1 cells by examining their viability, membrane integrity, levels of cytokine and ROS production, phagocytosis, and cytometric apoptosis. Moreover, as an extended study, a toxicity evaluation in the acute and chronic phases was performed in mice via intravenous injection of the materials. GOs exhibited dose- and size-dependent toxicity. Interestingly, SLGO induced ROS production to a lesser extent than MLGO. Cytometric analysis indicated that SLGO induced necrosis and apoptosis to a lesser degree than MLGO. In addition, cell damage and IL-1β production were influenced by phagocytosis. A histological animal study revealed that GOs of various sizes induced acute and chronic damage to the lung and kidney in the presence or absence of Pluronic F-127. These results will facilitate studies of GO prior to its biomedical application.
The effect of poly-γ-glutamic acid (γPGA), which is produced by Bacillus sp., on the production of recombinant erythropoietin (rEPO) by Chinese hamster ovary (CHO) cells in suspension culture was evaluated. The growth, viability, and productivity of recombinant CHO cells were investigated in a chemically defined medium with 50 and 500 kD γPGAs at 0.075% or with Pluronic F68. Cell growth with the two γPGAs was lower than that with Pluronic F68 but significantly higher than that without any additive (control). The effect of additives on rEPO productivity was 50 kDa γPGA > 500 kDa γPGA > Pluronic F68 > control. Using EPO-dependent F-36E cells, we found that the effect of additives on rEPO quality was 500 kDa γPGA > 50 kDa γPGA > control > Pluronic F68. γPGA has an enhancement effect on the quality of rEPO produced by CHO cells.
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