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Comparative sensitivity of tumor and non-tumor cell lines as reliable approach for in vitro cytotoxicity screening of lysine-based surfactants with potential pharmaceutical applications

机译:肿瘤和非肿瘤细胞系的比较敏感性,作为基于赖氨酸的表面活性剂的体外细胞毒性筛选的可靠方法,具有潜在的药物应用

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摘要

Surfactants are used as additives in topical pharmaceuticals and drug delivery systems. The biocompatibility of amino acid-based surfactants makes them highly suitable for use in these fields, but tests are needed to evaluate their potential toxicity. Here we addressed the sensitivity of tumor (HeLa, MCF-7) and non-tumor (3T3, 3T6, HaCaT, NCTC 2544) cell lines to the toxic effects of lysine-based surfactants by means of two in vitro endpoints (MTT and NRU). This comparative assay may serve as a reliable approach for predictive toxicity screening of chemicals prior to pharmaceutical applications. After 24-h of cell exposure to surfactants, differing toxic responses were observed. NCTC 2544 and 3T6 cell lines were the most sensitive, while both tumor cells and 3T3 fibroblasts were more resistant to the cytotoxic effects of surfactants. IC50-values revealed that cytotoxicity was detected earlier by MTT assay than by NRU assay, regardless of the compound or cell line. The overall results showed that surfactants with organic counterions were less cytotoxic than those with inorganic counterions. Our findings highlight the relevance of the correct choice and combination of cell lines and bioassays in toxicity studies for a safe and reliable screen of chemicals with potential interest in pharmaceutical industry.
机译:表面活性剂在局部药物和药物递送系统中用作添加剂。氨基酸表面活性剂的生物相容性使其非常适合在这些领域中使用,但需要进行测试以评估其潜在的毒性。在这里,我们通过两个体外终点(MTT和NRU)解决了肿瘤细胞(HeLa,MCF-7)和非肿瘤细胞(3T3、3T6,HaCaT,NCTC 2544)对赖氨酸表面活性剂的毒性的敏感性)。该比较测定法可作为可靠的方法,用于在药物应用之前进行化学物质的预测毒性筛选。细胞暴露于表面活性剂24小时后,观察到不同的毒性反应。 NCTC 2544和3T6细胞系最敏感,而肿瘤细胞和3T3成纤维细胞对表面活性剂的细胞毒性作用更具抵抗力。 IC50值表明,无论化合物或细胞系如何,通过MTT分析比通过NRU分析更早检测到细胞毒性。总体结果表明,具有有机抗衡离子的表面活性剂比具有无机抗衡离子的表面活性剂具有更低的细胞毒性。我们的发现强调了在毒性研究中正确选择细胞系和进行生物测定的组合的相关性,可以安全,可靠地筛选对制药业具有潜在兴趣的化学物质。

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