Supramolecular formulation of Nitidine chloride (cas 13063-04-2) can alleviate its hepatotoxicity and improve its anticancer activity

Add time:09/24/2019    Source:sciencedirect.com

Nitidine chloride (cas 13063-04-2) (NC) has demonstrated promising anticancer activity. However, NC has also shown non-specific 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 ([email protected][7]) complexes was characterized by 1H nuclear magnetic resonance and Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction analysis. As a consequence of the supramolecular complexation, [email protected][7] showed significantly lower toxicity (IC50: 6.87 ± 0.80 μM) on a liver cell line (LO2), and higher cytotoxicity (IC50: 2.94 ± 0.15 μM) on a breast cancer cell line (MCF-7), when compared with the free drug (IC50 of 3.48 ± 0.49 μM and 7.28 ± 0.36 μM, 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.

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