Evaluation of the Anti-Tumor Activity of Niclosamide Nanoliposomes Against Colon Carcinoma

Background and Aims: Niclosamide is an established anti-helminthic drug, which has recently been shown to inhibit the growth of various cancer cells. To exploit the potential anti-tumor activity of this drug for systemic use, the problem of low aqueous solubility should be addressed. The present study tested the in vivo anti-tumor effects of a recently developed nanoliposomal preparation of niclosamide in an experimental model of colon carcinoma. Methods: The cytotoxicity of nanoliposomal niclosamide on CT26 colon carcinoma cells was evaluated using the MTT test. Inhibition of tumor growth was investigated in BALB/c mice bearing CT26 colon carcinoma cells. The animals were randomly divided into 4 groups including: 1) untreated control, 2) liposomal doxorubicin (15 mg/kg; single intravenous dose), 3) liposomal niclosamide (1 mg/kg/twice a week; intravenously for 4 weeks), and 4) free niclosamide (1 mg/kg/twice a week; intravenously for 4 weeks). To study therapeutic efficacy, tumor size and survival were monitored in 2-day intervals for 40 days. Results: In vitro results indicated that nanoliposomal and free niclosamide could exert cytotoxic effects with IC50 values of 4.5 and 2.5 μM, respectively. According to in vivo studies, nanoliposomal niclosamide showed a higher growth inhibitory activity against CT26 colon carcinoma cells compared with free niclosamide as revealed by delayed tumor growth and prolongation of survival. Conclusion: Nnaoliposomal encapsulation enhanced anti-tumor properties of niclosamide in an experimental model of colon carcinoma.