Kaya Ayşe, Arafat Basel, Chichger Havovi, Tolaymat Ibrahim, Pierscionek Barbara, Khoder Mouhamad, Najlah Mohammad
Pharmaceutical Research Group, School of Allied Health, Faculty of Health, Medicine and Social Care, Medical Technology Research Centre, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, UK.
Biomedical Research Group, School of Life Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UK.
Pharmaceutics. 2023 Dec 31;16(1):65. doi: 10.3390/pharmaceutics16010065.
Zinc diethyldithiocarbamate (Zn (DDC)), a disulfiram metabolite (anti-alcoholism drug), has shown a strong anti-cancer activity in vitro. However, its application was limited by its low aqueous solubility and rapid metabolism. In this study, the solubility enhancement of Zn (DDC) is investigated by forming inclusion complexes with cyclodextrins. The inclusion complexes were prepared using two different types of beta-cyclodextrins, SBE-CD and HP-CD. Phase solubility diagrams for the resulting solutions were assessed; subsequently, the solutions were freeze-dried for further characterisation studies using DSC, TGA, XRD, and FTIR. The cytotoxic activity of the produced inclusion complexes was evaluated on human lung carcinoma cells using the MTT assay. The solubility of Zn (DDC) increased significantly upon adding beta-cyclodextrins, reaching approximately 4 mg/mL for 20% / CD solutions. The phase solubility diagram of Zn (DDC) was of the Ap-type according to the Higuchi and Connors model. Characterisation studies confirmed the inclusion of the amorphous drug in the CD-Zn (DDC) complexes. The cytotoxicity of Zn (DDC) was enhanced 10-fold by the inclusion complexes compared to the free drug. Overall, the resulting CD-Zn (DDC) inclusion complexes have a potential for treatment against lung cancer.
二乙基二硫代氨基甲酸锌（Zn (DDC)），一种双硫仑代谢物（抗酒精中毒药物），在体外已显示出强大的抗癌活性。然而，其应用受到低水溶性和快速代谢的限制。在本研究中，通过与环糊精形成包合物来研究Zn (DDC) 的溶解度增强情况。使用两种不同类型的β-环糊精，即磺丁基醚-β-环糊精（SBE-CD）和羟丙基-β-环糊精（HP-CD）制备包合物。评估所得溶液的相溶解度图；随后，将溶液冷冻干燥以使用差示扫描量热法（DSC）、热重分析法（TGA）、X射线衍射法（XRD）和傅里叶变换红外光谱法（FTIR）进行进一步的表征研究。使用MTT法在人肺癌细胞上评估所制备包合物的细胞毒性活性。加入β-环糊精后，Zn (DDC) 的溶解度显著增加，对于20% / CD溶液达到约4 mg/mL。根据Higuchi和Connors模型，Zn (DDC) 的相溶解度图为Ap型。表征研究证实了无定形药物包含在CD-Zn (DDC) 复合物中。与游离药物相比，包合物使Zn (DDC) 的细胞毒性增强了10倍。总体而言，所得的CD-Zn (DDC) 包合物具有治疗肺癌的潜力。
