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

// Chi-Kang Lin 1, 2 , Meng-Yi Bai 3 , Teh-Min Hu 4 , Yu-Chi Wang 1, 2 , Tai-Kuang Chao 5 , Shao-Ju Weng 1, 6 , Rui-Lan Huang 7, 8 , Po-Hsuan Su 7, 8 , Hung-Cheng Lai 1, 7, 8 1 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan 2 Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan 3 Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan 4 School of Pharmacy, National Defense Medical Center, Taipei, Taiwan 5 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 6 Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan 7 Department of Obstetrics and Gynecology, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan 8 Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Correspondence to: Hung-Cheng Lai, e-mail: hclai30656@gmail.com Keywords: nanoformulation, nanomedicine, niclosamide, ovarian cancer, cancer metabolism Received: September 07, 2015 Accepted: January 18, 2016 Published: February 01, 2016 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.