Diethyldithiocarbamate Copper II (DDC-Cu) has shown potent anticancer activity against a wide range of cancer cells, but further investigations are hindered by its practical insolubility in water. In this study, inclusion complexes of DDC-Cu with hydroxypropyl beta-cyclodextrin (HP) or sulfobutyl ether beta-cyclodextrin (SBE) were prepared and investigated as an approach to enhance the apparent solubility of DDC-Cu. Formulations were prepared by simple mixing of DDC-Cu with both cyclodextrin (CDs) at room temperature. Phase solubility assessments of the resulting solutions were performed. DDC-Cu CD solutions were freeze-dried for further characterisations by DSC, thermogravimetric analysis (TGA) and FT-IR. Stability and cytotoxicity studies were also performed to investigate the maintenance of DDC-Cu anticancer activity. The phase solubility profile deviated positively from the linearity (Ap type) showing significant solubility enhancement of the DDC-Cu in both CD solutions (approximately 4 mg/mL at 20% w/w CD solutions). The DSC and TGA analysis confirmed the solid solution status of DDC-Cu in CD. The resulting solutions of DDC-Cu were stable for 28 days and conveyed the anticancer activity of DDC-Cu on chemoresistant triple negative breast cancer cell lines, with IC₅₀ values less than 200 nM. Overall, cyclodextrin DDC-Cu complexes offer a great potential for anticancer applications, as evidenced by their very positive effects against chemoresistant triple negative breast cancer cells.

中文翻译：

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环糊精二乙基二硫代氨基甲酸酯铜II包合物：对化学抗性三阴性乳腺癌细胞系的有前途的化学传递系统。

二乙基二硫代氨基甲酸酯铜II（DDC-Cu）对多种癌细胞均显示出有效的抗癌活性，但由于其在水中的实际不溶性，进一步的研究受到了阻碍。在这项研究中，制备了DDC-Cu与羟丙基β-环糊精（HP）或磺丁基醚β-环糊精（SBE）的包合物，并以此作为提高DDC-Cu表观溶解度的方法。通过在室温下将DDC-Cu与两种环糊精（CD）简单混合来制备制剂。对所得溶液进行相溶解度评估。将DDC-Cu CD溶液冷冻干燥，以通过DSC，热重分析（TGA）和FT-IR进行进一步表征。还进行了稳定性和细胞毒性研究，以研究DDC-Cu抗癌活性的维持情况。w / w CD解决方案）。DSC和TGA分析证实了DDC-Cu在CD中的固溶状态。所得的DDC-Cu溶液稳定28天，并传达了DDC-Cu对化学抗性三阴性乳腺癌细胞系的抗癌活性，IC ₅₀值小于200 nM。总体而言，环糊精DDC-Cu复合物为抗癌应用提供了巨大潜力，其对化学耐药性三阴性乳腺癌细胞的非常积极的作用证明了这一点。