Development, Characterization and Evaluation of In Vivo Anti-Tumor Activity of Niclosamide Nanoliposomes Against Colon Carcinoma

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Author(s): Mahdi Hatamipour, Mahmoud R. Jaafari, Amir Abbas Momtazi-Borojeni, Mahin Ramezani, Amirhossein Sahebkar*.

Journal Name: Current Molecular Pharmacology

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Background and Aims: Niclosamide (Nic), an old FDA-approved anti-helminthic drug, has recently been shown to inhibit growth of various cancer cells. However, this drug shows a low aqueous solubility restricting its systemic use. The present study was aimed to prepare and characterize niclosamide nanoliposomes and evaluate their in vivo anti-tumor effects.

Methods: Nanoliposomes composed of hydrogenated soya phosphatidylcholine (HSPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy (polyethylene glycol)-2000] (DSPE) were prepared using lipid-film hydration method and Nic was encapsulated with remote loading method. The prepared nanoliposomes were characterized through visualizing morphology and measuring particle size and Zeta potential. HPLC analysis was used to quantify encapsulated Nic. The in vitro cytotoxicity of the nanoliposomal Nic on CT26 colon carcinoma cells was evaluated. Inhibition of tumor growth was investigated in BALB/c mice bearing CT26 colon carcinoma cells.

Results: Analytical results revealed that the nanoliposomal system was a homogeneous and stable colloidal dispersion of Nic particles. Atomic force microscopy images and particle size analysis indicated that all Nic particles had a spherical shape with a diameter of approximately 108 nm. According to in vitro and in vivo studies, nanoliposomal Nic showed a higher growth inhibitory activity against CT26 colon carcinoma cells compared with free Nic.

Conclusion: Encapsulation of Nic in liposome nanoparticles elevated its aqueous solubility, which was accompanied by enhanced anti-tumor properties in vivo.

Keywords: Liposome, Niclosamide, Remote-loading, Colon carcinoma, CT26 , vivo studies

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(E-pub Ahead of Print)
DOI: 10.2174/1874467212666190821142721
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