Master Degree / Yüksek Lisans Tezleri

Permanent URI for this collectionhttps://hdl.handle.net/11147/3008

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Department: search.filters.department.Thesis (Master)--İzmir Institute of Technology, BioengineeringSubject: search.filters.subject.Doxorubicin

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Now showing 1 - 5 of 5
  • Master Thesis
    Development of Doxorubicin-Loaded Liposomes Self-Assembled With Polysaccharides for Breast Cancer Therapy
    (01. Izmir Institute of Technology, 2023) Kılıç Özdemir, Sevgi; Polat, Hürriyet; Kılıç Özdemir, Sevgi; Polat, Hürriyet; 04.01. Department of Chemistry; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of Technology
    This thesis aimed to develop Tariquidar and Doxorubicin-loaded liposomes decorated by Fucoidan coating for breast cancer treatment. Fucoidan is a negatively charged polysaccharide with a special affinity to p-selectins expressed on MDA-MB-231 breast cancer cells and, at the same time, possesses anti-cancer activity. Different liposomes were prepared by extrusion method from the DSPC, Cholesterol, and cationic lipid DSTAP mixtures for coating negatively charged Fucoidan. The most stable liposomes with a size of 200 nm were obtained at a molar ratio of DSPC/Cholesterol/DSTAP:55/30/15, exhibiting a zeta potential above +30 mV. Tariquidar was encapsulated into the liposome bilayer by passive loading, and Doxorubicin into the core of the liposome by active loading. In the final step, liposomes were coated with Fucoidan by electrostatic interaction. Tariquidar loading was determined by UV-Vis spectrophotometry, indicating an optimum TRQ/Lipid molar ratio of 0.012 with encapsulation and loading efficiencies of 50% and 20%, respectively. Fluorescence spectrophotometry determined Doxorubicin loading, showing insignificant encapsulation efficiency change (exhibiting around 70%) by neither Tariquidar content in the bilayer nor DSTAP% in the formulation. An optimum amount of Fucoidan was determined by incubating the liposomes with varying amounts of fucoidan at different dilutions. Size and zeta potential measurements monitored the coating of liposomes with Fucoidan. Our finding showed that zeta potentials of liposomes go from positive to negative with increasing fucoidan, while no trend was observed in the size of liposomes. However, smaller sizes were observed when incubation was performed in diluted solutions.
  • Master Thesis
    Enhancement of Bioavailability of Vitamin D by Nano-Sized Delivery Systems
    (01. Izmir Institute of Technology, 2023) Bulmuş Zareie, Volga; Kılıç Özdemir, Sevgi; Kılıç Özdemir, Sevgi; Bulmuş Zareie, Esma Volga; 03.01. Department of Bioengineering; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Studies have indicated that Vitamin D (VitD) may decrease tumor invasiveness and propensity to metastasize. Cholecalciferol (VitD3) is the passive form of VitD3 and converts to active calcitriol through two-step hydroxylation reactions in the body, promoting binding to VitD-receptors (VDR). However, some breast cancer cells, especially MDA-MB-231, have very low levels of VDR. Besides, VitD3 suffers from first pass-effect of the liver which causes deactivation of VitD3. Therefore, new approaches are needed to increase VitD3 level in the cancerous sites. In this study, VitD3 was loaded into liposomes, which were subsequently coated by Fucoidan (FUC) to promote their binding to MDA-MB-231 cancer cells. Fucoidan strongly binds to P-selectins overexpressed in the breast cancer cells, blocking the cancer cells to adhere on the platelets to carry within the body, causing metastasis. Doxorubicin (DOX), being considered as the one of the most effective chemotherapeutic agents against breast cancer, was also loaded into liposomes in a similar manner. By liposomal encapsulations and fucoidan coating, it was aimed to deliver the all-cargo directly to the cancerous site and enhance the bioavailability of both agents at the target site. It was seen that liposomal VitD3 was more effective than free form to inhibit cell proliferation and, therapeutic potential of DOX increased with VitD3.VitD3 loaded FUC coated liposomes at optimized concentrations has a comparable effect with DOX-loaded liposomes with and without FUC coating. Overall, these results suggested that VitD3 and DOX loaded and FUC coated liposomes can be applied as combined therapy in cancer treatment.
  • Master Thesis
    Lab-on-a-chip devices for drug screening
    (Izmir Institute of Technology, 2019) Gökçe, Begüm; Pesen Okvur, Devrim; Çağır, Ali; Pesen Okvur, Devrim; Çağır, Ali; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    Breast cancer is one of the cancers with the highest incidence and mortality rates in women in Turkey as well as in the world. Tumor micro environment comprises of cancer and normal cells, extracellular matrix, soluble biological and chemical factors. Research has shown that cell shape, adhesion, migration, response to growth factors and drugs are different in 2D and 3D culture. Today, only 8 out of 100 anti-cancer clinical trial gives effective results. 3D cell culture systems have shown to be a necessary step between in vitro, in vivo and clinical studies. Therefore, it is necessary to better understand the interactions of cancer cells with their micro environment, for which new cell culture setups are required. The most apparent disadvantage of widely used 3D cell culture setups is the lack of stromal cells. The systems to be developed should both provide a 3D environment and comprise multiple cell types. The drug screen in 3D tri-culture method with a lab-on-a-chip device, that will be developed in this study will be able to answer these needs. Cell lines that represent different breast cancer types alone or together with stromal cells were cultured in 3D in the to be developed lab-on-a-chip; by determining the effects of drugs with different targets on the viability and distribution of cells, a drug screening method is developed.
  • Master Thesis
    Development of Drug-Loaded Microbubbles for In-Vitro Applications in Cell Biology
    (Izmir Institute of Technology, 2017) Coşkun, Sema; Özdemir, Ekrem; Özdemir, Ekrem; Sultan Altun, Zekiye; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Doxorubicin (DOX) is one of the drugs for cancer therapy. When DOX is used in solution, it affects not only the cancer cells but also the healthy cells. In order to eliminate possible side effects, DOX was encapsulated within liposomes and applied for the cancer therapy. Because the circulation time for liposomes is longer in the body, they accumulate in capillaries, especially at the finger tips and at the toe of the foot called the hand-and-foot syndrome. Here, we proposed to couple the liposomes containing DOX with the microbubbles as the ultrasound contrast agent and deliver the drug to the area of interest. Therefore, DOX was loaded within the liposomes and characterized for their DOX contents. The DOX containing liposomes were conjugated with microbubbles through the avidin-biotin chemistry. It was found that the loaded- DOX content within the liposomes was Langmuir-type. The loaded DOX content increased at lower DOX concentrations and leveled off at higher DOX concentrations. The Langmuir constants can be used in designing DOX loading experiments. The DOX containing liposomes were coupled with the microbubbles and found an optimum of 7.0 for the avidin/biotin mole ratio on the microbubbles. At the optimum avidin/biotin ratio, the conjugated lipo-DOX amount was 3×10-8 μg-DOX/MB. It was concluded that the DOX molecules can be loaded within the liposomes and easily conjugated with the microbubbles and employed in cancer treatments.
  • Master Thesis
    Comparison Od Side Effects of Anti-Cancer Drugs in 2d and 3d And, Classical and Cell-On Cultures
    (Izmir Institute of Technology, 2016) Kankale, Deniz; Çağır, Ali; Pesen Okvur, Devrim; Pesen Okvur, Devrim; Çağır, Ali; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    The studies that aim to assess the effects of drugs developed against cancer at the cellular level use multiwell plates. However, these classical systems fail to reproduce the in-vivo like microenvironment necessary for realistic assessment. In addition, classical cell culture systems use high amount of materials increasing cost. On the other hand, lab-on-a-chip systems use minimal volumes of reagents and more importantly can mimic the in-vivo microenvironment via spatial and temporal control. Furthermore, it is known that cell response to drugs can be very different in 2D and 3D cell culture setups. Doxorubicin is a widely used anticancer drug. Here, doxorubicin uptake by highly metastatic human breast cancer cell line MDA-MB-231 and normal mammary epithelial cell line MCF10A were investigated using 2D and 3D, classical and cell-on-a-chip cultures. Drug uptake at 24, 48 and 72 hours various concentrations of the drug determined by measuring signal intensities from fluorescence microscopy images of cells. For cell viability assay, cells were stained with dapi and two cell lines were compared in systems. According to results, it was observed that 3D cell culture environment in chip provides more in-vivo like environment with less reagent consumption and cell viability is not correlated only with drug uptake.