Chitosan coated lipid carriers as nanoplatform for repurposed anti-breast cancer activity of niclosamide

Drug repurposing is promising strategy with niclosamide showing encouraging results against breast cancer. However, niclosamide hydrophobicity limits its oral bioavailability and minimizes its anti-cancer activity. Nano-structured lipid carriers (NLCs) showed enhance therapeutic performance coping formulation limitations of insoluble drugs. The present work investigated NLCs and chitosan coated NLCs for oral delivery of niclosamide in treatment of breast cancer. NLCs comprised precirol ATO 5 and compritol 888 ATO as solid lipids, oleic acid and Tween 80 as liquid components and dicetyl phosphate as charging agent to allow coating. NLCs were prepared by micro-emulsification technique and characterized by dynamic light scattering spectroscopy, transmission electron microscopy in addition to determination of the entrapment efficiency, drug loading and release.

Furthermore, the in vivo efficacy of niclosamide was investigated employing Solid Ehrlich Carcinoma bearing mice model. This involved determination of tumor growth activity which was further verified by histopathological examination. Combined characterization results indicated the development of NLCs and chitosan coated NLCs with size ranging from 189.6 to 334.5nm. The entrapment efficiency was higher than 98 % with slow drug release being noticed. Additionally, uncoated and coated NLCs formulations effectively enhanced the anti-proliferative activity of niclosamide compared to drug suspension with chitosan coated NLCs being superior.

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Materials

Niclosamide was obtained as a gift sample from Alexandria Pharmaceuticals, Alexandria, Egypt. Precirol ATO 5 (glyceryl distearate) and compritol 888 ATO (glyceryl behenate) were provided as a gift samples by Gattefosse, Lyon, France. Oleic acid, sodium tri polyphosphate, dicetyl phosphate and dialysis tubing cellulose membrane (molecular weight cutoff 14.000 Daltons) were purchased from Sigma Aldrich, St. Louis, MO, USA. Tween 80, potassium dihydrogen phosphate, potassium hydroxide

Nancy E. Elkholy, Amal A. Sultan, Sally E. Abu-Risha, Gamal M. El Maghraby, Chitosan coated lipid carriers as nanoplatform for repurposed anti-breast cancer activity of niclosamide, Journal of Drug Delivery Science and Technology, 2024, 105414, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2024.105414.