Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer
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Chi-Kang Lin1,2, Meng-Yi Bai3, Teh-Min Hu4, Yu-Chi Wang1,2, Tai-Kuang Chao5, Shao-Ju Weng1,6, Rui-Lan Huang7,8, Po-Hsuan Su7,8, Hung-Cheng Lai1,7,8
1Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
2Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan
3Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan
4School of Pharmacy, National Defense Medical Center, Taipei, Taiwan
5Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
6Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan
7Department of Obstetrics and Gynecology, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
8Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Hung-Cheng Lai, e-mail: firstname.lastname@example.org
Keywords: nanoformulation, nanomedicine, niclosamide, ovarian cancer, cancer metabolism
Received: September 07, 2015 Accepted: January 18, 2016 Published: February 01, 2016
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.
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