Department of Physical Chemistry and Technology of Polymers, Faculty of Chemistry, Silesian University of Technology, 44-100 Gliwice, Poland.
Department of Systems Biology and Engineering, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, Poland.
Int J Mol Sci. 2021 Jul 20;22(14):7741. doi: 10.3390/ijms22147741.
In vitro cytotoxicity of polymer-carriers, which in the side chains contain the cholinum ionic liquid units with chloride (Cl) or pharmaceutical anions dedicated for antituberculosis therapy, i.e., -aminosalicylate (PAS) and clavulanate (CLV), was investigated. The carriers and drug conjugates were examined, in the concentration range of 3.125-100 μg/mL, against human bronchial epithelial cells (BEAS-2B) and adenocarcinomic human alveolar basal epithelial cells (A549) as an experimental model cancer cell line possibly coexisting in tuberculosis. The cytotoxicity was evaluated by MTT test and confluency index, as well as by the cytometric analyses, including Annexin-V FITC apoptosis assay. The polymer systems showed supporting activity towards the normal cells and no tumor progress, especially at the highest concentration (100 μg/mL). The analysis of cell death did not show meaningful changes in the case of the BEAS-2B, whereas in the A549 cell line, the cytostatic activity was observed, especially for the drug-free carriers, causing death in up to 80% of cells. This can be regulated by the polymer structure, including the content of cationic units, side-chain length and density, as well as the type and content of pharmaceutical anions. The results of MTT tests, confluency, as well as cytometric analyses, distinguished the polymer systems with Cl/PAS/CLV containing 26% of grafting degree and 43% of ionic units or 46% of grafting degree and 18% of ionic units as the optimal systems.
研究了在侧链中含有氯离子（Cl）或专门用于抗结核治疗的药物阴离子（-氨基水杨酸酯（PAS）和克拉维酸（CLV）的季铵离子液体单元的聚合物载体的体外细胞毒性。在 3.125-100 μg/mL 的浓度范围内，对人支气管上皮细胞（BEAS-2B）和人肺泡基底腺癌细胞（A549）进行了载体和药物缀合物的检测，作为可能与结核病共存的实验性癌细胞系。通过 MTT 试验和细胞融合指数以及流式细胞术分析，包括 Annexin-V FITC 凋亡测定法，评估了细胞毒性。聚合物系统对正常细胞具有支持活性，并且没有肿瘤进展，尤其是在最高浓度（100 μg/mL）下。BEAS-2B 细胞中细胞死亡的分析没有显示出有意义的变化，而在 A549 细胞系中观察到细胞抑制活性，特别是对于无药物载体，导致多达 80％的细胞死亡。这可以通过聚合物结构来调节，包括阳离子单元的含量、侧链长度和密度以及药物阴离子的类型和含量。MTT 试验、细胞融合以及流式细胞术分析的结果区分了含有 26％接枝度和 43％离子单元或 46％接枝度和 18％离子单元的 Cl/PAS/CLV 聚合物系统为最佳系统。
