Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India.
National Centre for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500007, India.
Carbohydr Polym. 2019 May 15;212:252-259. doi: 10.1016/j.carbpol.2019.02.041. Epub 2019 Feb 13.
Niclosamide, previously used as an anthelmintic drug is currently being repurposed for its anticancer activity. Niclosamide is a brick like biopharmaceutical classification system (BCS) class II drug with poor aqueous solubility and dissolution consequently leading to low bioavailability. By considering the physicochemical properties and geometry of niclosamide, inclusion complex with cyclodextrin was prepared by freeze drying method and characterized using FT-IR, DSC, PXRD, and HNMR. In silico molecular modeling study was performed to study the possible interactions between niclosamide and cyclodextrin. The anticancer activity of niclosamide formulation was evaluated through in vitro cell cytotoxicity study using various cancer cell lines. The potential of niclosamide complex for improvement of the bioavailability was evaluated in male BALB/c mice. In vitro cytotoxicity studies indicated significantly higher cytotoxicity at lower concentrations and the pharmacokinetic studies showed significant improvement in C and T of niclosamide from cyclodextrin complex in comparison to pure niclosamide alone.
尼氯硝唑，先前被用作驱虫药，目前正因其抗癌活性而被重新用于其他用途。尼氯硝唑是一种块状的生物制药分类系统（BCS）Ⅱ类药物，水溶性和溶解性能差，导致生物利用度低。考虑到尼氯硝唑的物理化学性质和几何形状，通过冷冻干燥法制备了与环糊精的包合物，并通过 FT-IR、DSC、PXRD 和 HNMR 进行了表征。进行了计算机分子建模研究，以研究尼氯硝唑和环糊精之间可能的相互作用。通过使用各种癌细胞系进行体外细胞细胞毒性研究评估了尼氯硝唑制剂的抗癌活性。在雄性 BALB/c 小鼠中评估了尼氯硝唑复合物提高生物利用度的潜力。体外细胞毒性研究表明，在较低浓度下具有更高的细胞毒性，药代动力学研究表明，与单独使用纯尼氯硝唑相比，尼氯硝唑环糊精复合物的 C 和 T 有显著改善。
