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Supramolecular formulation of nitidine chloride can alleviate its hepatotoxicity and improve its anticancer activity

Abstract : Nitidine chloride (NC) has demonstrated promising anticancer activity. However, NC has also shown nonspecific toxicity in various healthy organs such as the liver. In this study, we aimed to develop a supramolecular formulation of NC and investigate the associated benefits of such a supramolecular formulation on modulating its inherent hepatotoxicity and anticancer activity. The formation of NC-cucurbit[7]uil (NC@CB[7]) complexes was characterized by H-1 nuclear magnetic resonance and Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction analysis. As a consequence of the supramolecular complexation, NC@CB[7] showed significantly lower toxicity (IC50: 6.87 +/- 0.80 mu M) on a liver cell line (LO2), and higher cytotoxicity (IC50: 2.94 +/- 0.15 mu M) on a breast cancer cell line (MCF-7), when compared with the free drug (IC50 of 3.48 +/- 0.49 mu M and 7.28 +/- 0.36 mu M, on these two cell lines, respectively). Investigation of cellular uptakes revealed that CB[7]'s capability in modulating the toxicity/activity of NC was mainly attributed to the drug's different cellular uptake behaviors that were influenced by CB[7]'s complexation. Taken together, we have demonstrated that supramolecular formulation of NC by CB(7] significantly alleviated its hepatotoxicity and improved its anticancer activity in vitro. (C) 2017 Elsevier Ltd. All rights reserved.
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Submitted on : Monday, April 23, 2018 - 2:41:17 PM
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Wanying Li, Hang Yin, David Bardelang, Jianbo Xiao, Ying Zheng, et al.. Supramolecular formulation of nitidine chloride can alleviate its hepatotoxicity and improve its anticancer activity. Food and Chemical Toxicology, Elsevier, 2017, 109, pp.923--929. ⟨10.1016/j.fct.2017.02.022⟩. ⟨hal-01774177⟩



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