| Status | 已發表Published |
| Supramolecular inclusion of nitidine chloride reduced its hepatotocixity and improved its anticancer activity | |
Li, W. ; Ying, H.; Bardelang, D.; Zheng, Y. ; Wang, R.
| |
| 2016-11-19 | |
| Source Publication | 2016 Chinese Pharmaceutical Conference
 |
| Abstract | Nitidine chloride (NC), a natural alkaloid isolated from the root of Zanthoxylum nitidum, has demonstrated promising anticancer activity against various types of cancer. However, NC has also shown non-specific toxicity in various healthy organs such as liver. In this study, we aimed to develop a supramolecularly formulated NC and investigate the associated benefits of such a supramolecular inclusion of the drug on its inherent hepatotoxicity and anticancer activity. The formation of NC@CB[7] was confirmed by proton nuclear magnetic resonance (1H NMR) and Fourier Transform infrared (FTIR) spectroscopy. NC@CB[7] showed excellent thermal stability which was characterized by differential scanning calorimetry (DSC), providing a more stable drug product. The cytotoxicity of the free NC and NC@CB[7] was evaluated by MTT assay on both a normal human liver cell line (LO2) and a breast cancer cell line (MCF-7). Interestingly, NC@CB[7] showed obviously lower toxicity on the normal liver cell, and higher toxicity on the breast cancer cell, when compared with those of the free drug. The IC50 value of NC@CB[7] on MCF-7 cell line was 2.94 ±0.15 μM, which was approximately 60% lesser than that of NC (7.28± 0.36 μM). On the other hand, the IC50 values of NC and NC@CB[7] were 3.48 ± 0.49 μM and 6.87±0.80 μM respectively, indicating that CB[7] significantly decreased the toxicity of NC on LO2 cell line. NC@CB[7] was further investigated by a cellular uptake study, showing that the changed toxicity of NC@CB[7] was associated with respective cellular uptake. In particular, NC@CB[7] complexes exhibited a 2.1-fold increase in cellular uptake when compared with free drug at 0.5 h of incubation, suggesting that NC@CB[7] can be more readily internalized by breast cancer cells. Conversely, the cellular uptake of NC@CB[7] in LO2 cell was lower than free drug across all the time points, which account for the reduced hepatotoxicity of NC@CB[7]. A clonogenic assay further confirmed that NC@CB[7] possessed superior anticancer activity on the breast cancer cell line than the free drug. Taken together, we have demonstrated that supramolecular inclusion of NC by CB[7] decreased its hepatotoxicity and improved its anticancer activity in vitro. |
| Keyword | Nitidine chloride |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 40851 |
| Document Type | Conference paper |
| Collection | DEPARTMENT OF PHARMACEUTICAL SCIENCES |
| Corresponding Author | Zheng, Y.; Wang, R. |
| Recommended Citation GB/T 7714 | Li, W.,Ying, H.,Bardelang, D.,et al. Supramolecular inclusion of nitidine chloride reduced its hepatotocixity and improved its anticancer activity[C], 2016. |
| APA | Li, W.., Ying, H.., Bardelang, D.., Zheng, Y.., & Wang, R. (2016). Supramolecular inclusion of nitidine chloride reduced its hepatotocixity and improved its anticancer activity. 2016 Chinese Pharmaceutical Conference. |
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