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    Development of A Novel Liposomal Formulation of a Pyridine Chalcone Analogue for HER-2 Positive Breast Cancer

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    Sara Abdulkader_ OGS Approved Thesis.pdf (2.189Mb)
    Date
    2024-01
    Author
    Abdulkader, Sara
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    Abstract
    Breast cancer is the most prevalent cancer in women and the fifth leading cause of death due to cancer worldwide. Human epidermal growth factor receptor-2 (HER-2) is an oncoprotein that is overexpressed in 25-30% of breast cancer cases, and it is attributed to the poor prognosis of the disease. The currently available treatments for HER-2 positive breast cancer are associated with drug resistance, recurrence, and severe adverse drug events. Therefore, there is an urgent need to develop new treatments for this type of cancer. A thienyl pyridine chalcone analogue compound (OH-25) was discovered in our lab and it produced a good anticancer activity against prostate cancer. However, OH-25 is extremely lipophilic and insoluble in water. Therefore, liposomes are used as a drug delivery system to improve the water solubility of OH-25. Liposomes were prepared using thin film hydration method and probe sonication was used to reduce the particle size to nano-size. The prepared formulations were characterized by evaluating particle size, polydispersity index, and zeta potential using Malvern zeta sizer, while entrapment efficiency was evaluated using reversed phase-high performance liquid chromatography. The anticancer activity of OH-25 and its liposomal formulation that was prepared using a 1:1 mole ratio of lipid and 5% of OH-25 was screened against two HER-2 positive breast cancer cell lines (SK-BR-3 and ZR-75) at two time points, and the results showed no statistically significant difference between the cytotoxicity of drug-loaded liposomes and free drug after 72 hours of treatment. Several biological evaluations were conducted, including morphological evaluation, migration assay, colony formation assay, and western blot analysis. The findings of the assays showed cytotoxicity, proapoptotic, antimigration, inhibition of colony formation, and inhibition of ERK1/2 signalling pathway by drug-loaded liposomes and free drug. In conclusion, liposomal formulation helped to improve water solubility and maintained the anticancer activity of OH-25 against cancer cells. Further biological evaluations are needed to identify the molecular pathways affected by those treatments and determine the selectivity index of liposomal formulations and free drug toward cancer cells.
    DOI/handle
    http://hdl.handle.net/10576/51511
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