Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer

Chi Kang Lin, Meng Yi Bai, Teh Min Hu, Yu Chi Wang, Tai Kuang Chao, Shao Ju Weng, Rui Lan Huang, Po Hsuan Su, Hung Cheng Lai

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26 Citations (Scopus)

Abstract

Ovarian cancer treatment remains a challenge and targeting cancer stem cells presents a promising strategy. Niclosamide is an "old" antihelminthic drug that uncouples mitochondria of intestinal parasites. Although recent studies demonstrated that niclosamide could be a potential anticancer agent, its poor water solubility needs to be overcome before further preclinical and clinical investigations can be conducted. Therefore, we evaluated a novel nanosuspension of niclosamide (nano-NI) for its effect against ovarian cancer. Nano-NI effectively inhibited the growth of ovarian cancer cells in which it induced a metabolic shift to glycolysis at a concentration of less than 3 μM in vitro and suppressed tumor growth without obvious toxicity at an oral dose of 100 mg/kg in vivo. In a pharmacokinetic study after oral administration, nano-NI showed rapid absorption (reaching the maximum plasma concentration within 5 min) and improved the bioavailability (the estimated bioavailability for oral nano-NI was 25%). In conclusion, nano-NI has the potential to be a new treatment modality for ovarian cancer and, therefore, further clinical trials are warranted.

Original languageEnglish
Pages (from-to)8993-9006
Number of pages14
JournalOncotarget
Volume7
Issue number8
DOIs
Publication statusPublished - 2016

Keywords

  • Cancer metabolism
  • Nanoformulation
  • Nanomedicine
  • Niclosamide
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Lin, C. K., Bai, M. Y., Hu, T. M., Wang, Y. C., Chao, T. K., Weng, S. J., Huang, R. L., Su, P. H., & Lai, H. C. (2016). Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer. Oncotarget, 7(8), 8993-9006. https://doi.org/10.18632/oncotarget.7113