Master in Pharmacy
http://hdl.handle.net/10576/3099
2024-03-30T02:33:01ZThe Cytotoxicity Of “Al-Siddir” Tree “Ziziphus Spina Christi” Methanolic Leaves Extract on Her-2 Positive Breast Cancer
http://hdl.handle.net/10576/51518
The Cytotoxicity Of “Al-Siddir” Tree “Ziziphus Spina Christi” Methanolic Leaves Extract on Her-2 Positive Breast Cancer
Saeed, Sumayyah Khaled Mohammad
HER-2 positive is a subtype of breast cancer that acquires poor prognosis and low survival rates. Targeted therapy is one of the main approaches that are used for the treatment of HER-2-positive breast cancer. However, it is associated with several adverse effects and a high chance of drug resistance, which necessitates continuous research to discover novel agents. Medicinal plants are a rich source of many biologically active ingredients that could be potential candidates for anticancer leads. Ziziphus spina-Christi (ZSC) is a plant species that exerts various biological activities, including cytotoxicity, as it contains different essential bioactive constituents.
This study is the first to investigate the cytotoxic potential of the methanolic leaves extract of ZSC that is growing in Qatar against HER-2 positive breast cancer cell lines SK-BR-3 and ZR-75-1 on the cellular and molecular levels using different in vitro assays as well as in ovo assay for angiogenesis evaluation using the chicken embryo model. The established ZSC methanolic leaves extract was standardized by RP-HPLC analysis using the flavonoids rutin and quercetin as marker compounds.
Biological evaluation revealed that ZSC extract had significantly reduced the viability, altered the morphological features of the cells, induced apoptosis, and inhibited the migration, colony formation, and angiogenesis in both cell lines. Moreover, molecular investigations had revealed that ZSC extract produced its effect by inactivating the HER-2 / p38 MAPK signaling pathway that is mainly involved in the carcinogenesis process and by deregulating different proteins such as Bax, E-cadherin, and NF-κB. These results collectively support the promising cytotoxic potential of ZSC against HER-2-positive breast cancer and allow a basis for further related investigations.
2024-01-01T00:00:00ZDeveloping Pharmacist-Led Anticoagulation Clinics in Primary Care Settings: A Multi-Phase Mixed-Methods Study
http://hdl.handle.net/10576/51517
Developing Pharmacist-Led Anticoagulation Clinics in Primary Care Settings: A Multi-Phase Mixed-Methods Study
Alshihab, Safaa Khalaf
Background: Primary care is an integral part of the healthcare system. Patients have better accessibility and continuity of care. However, studies have reported low-quality warfarin management in these settings. Pharmacist-led anticoagulation clinics have evolved as an effective practice to improve anticoagulation control. Pharmacists demonstrated better outcomes than usual care. Hence, we aimed to assess the rationale and feasibility of implementing a pharmacist-led anticoagulation clinic in the primary care settings in Qatar.
Methodology: A multiphase mixed-methods design was conducted between June and October 2023. The first phase was a retrospective study that assessed the quality of warfarin management by measuring the percentage of time-in-therapeutic range (TTR) and the percentage of extreme out-of-range INR readings. In phase two, a convergent mixed-methods study was conducted to explore the perception of key stakeholders about implementing the clinic and to determine the essential components of the clinic implementation. The quantitative strand explored the perceptions of patients, pharmacists, and physicians at PHCC through an online survey. The qualitative strand was a semi-structured interview with the key informant at the PHCC. Inferential and descriptive analyses were performed as appropriate.
Results: The mean (SD) TTR for the 494 patients included in the study was 45.33% (17.52%), which was lower than the recommended value of 70% (P<0.001). Both pharmacists and physicians have recognized the significance of the clinic. Patients generally have confidence in the service's ability to improve their health, with most believing that pharmacists would have the ability to provide safe and effective care. Key informants emphasized the importance of optimizing the management of patients on warfarin. They strongly believed in the proposed clinic to address the patients’ needs. The main identified facilitators were ensuring pharmacists’ competency and establishing effective communication. Staff shortages were identified as the primary obstacles to the clinic's implementation.
Conclusions: The findings of this study provide strong support for establishing a pharmacist-led anticoagulation clinic in primary care settings. Stakeholders believe that this model can serve as an effective strategy to address the existing shortcomings in anticoagulation management in primary care settings. Tailoring the service to the PHCC context, fully leveraging the strengths of facilitators, and overcoming obstacles are crucial to ensure the success of the clinic implementation.
2024-01-01T00:00:00ZNano Liposomal Formulation for A Novel Chalcone Compound as A Potential Anticancer Delivery System for Triple-Negative Breast Cancer
http://hdl.handle.net/10576/51516
Nano Liposomal Formulation for A Novel Chalcone Compound as A Potential Anticancer Delivery System for Triple-Negative Breast Cancer
Suliman, Azza
Triple negative breast cancer is the most aggressive type of breast malignancy accounting for 15-20% of all breast cancer cases. Treatment of TNBC remains limited, with a high risk of relapse and metastasis to other organs. On the other hand, compound DK14 has been identified and screened biologically and proven to be a potent anticancer agent against HER-2 positive and triple-negative breast cancers. However, like many other anticancer agents, compound DK14 has poor water solubility, hindering its further development. Hence, we developed a nano liposomal formulation encapsulating compound DK14 to enhance its solubility, safety, and anticancer activity. The liposomal formulation has been characterized by particle size, PDI, and zeta potential. Furthermore, DK14 EE% was found to have a high value of 89%. The pharmacological screening of DK14 liposomes has revealed that it has inhibited the proliferation of TNBC cell lines and induced clear morphological changes that indicate apoptosis. Moreover, DK14 liposomes have exhibited an enhanced safety profile on MCF-10A; in addition, it has demonstrated a higher selectivity towards TNBC cells over normal cells compared to the free drug. Furthermore, DK14 liposomes have inhibited the migration of TNBC cell lines and colony formation, indicating their ability to inhibit tumor growth and metastasis in vivo. The investigations of the molecular mechanisms by which DK14 liposomes have exerted their effects have revealed that DK14 liposomes have induced apoptosis via deregulation of the BAX/BCL-2/Caspase-3 pathway. Further, DK14 liposomes have downregulated the PI3K/AKT/mTOR pathway, which is defective in TNBC. The in ovo screening has revealed that DK14 liposomes have inhibited the angiogenesis of the CAM model. Our findings implied that DK14 liposomes have a substantial anticancer activity against TNBC and have provoked apoptosis via the PI3K/AKT/mTOR pathway.
Keywords: DK14 liposomes, TNBC, PI3K/AKT/mTOR pathway, Apoptosis, In ovo.
2024-01-01T00:00:00ZDevelopment of A Novel Liposomal Formulation of a Pyridine Chalcone Analogue for HER-2 Positive Breast Cancer
http://hdl.handle.net/10576/51511
Development of A Novel Liposomal Formulation of a Pyridine Chalcone Analogue for HER-2 Positive Breast Cancer
Abdulkader, Sara
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.
2024-01-01T00:00:00Z