Master Degree / Yüksek Lisans Tezleri

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

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Author: search.filters.author.Kılıç Özdemir, Sevgi

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Now showing 1 - 6 of 6
  • Master Thesis
    Development of Doxorubicin-Loaded Liposomes Self-Assembled With Polysaccharides for Breast Cancer Therapy
    (01. Izmir Institute of Technology, 2023) Önol, Ayşenur Başar; Kılıç Özdemir, Sevgi; Polat, Hürriyet
    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) Sağlam, Ezgi İrem; Kılıç Özdemir, Sevgi; Bulmuş Zareie, Esma Volga
    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
    Development of Ultrasound Triggered Drug Delivery Systems for Cancer Treatment
    (Izmir Institute of Technology, 2019) Önercan, Cansu; Kılıç Özdemir, Sevgi
    Doxorubicin (DOX) is one of the most commonly used hydrophilic anticancer drug in cancer treatment. However, when it is used in free form, it can attack not only cancer cells but also healthy cells. So as to prevent entering of DOX to the healthy cells, the encapsulation method is employed. Liposomes are suitable for encapsulation of DOX but the most important problems with the use of liposome are hand-foot syndrome and stomatitis. Encapsulation method is not enough because of these reasons, thus delivery of DOX to the desired site by targeted therapy has gained interest in recent years. In this study, DOX was encapsulated into liposomes and the DOX loaded liposomes (LipoDOX) was attached to microbubbles (MBs). MBs as ultrasound contrast agents are widely used in medical imaging. Use of MBs in combination of DOX loaded liposomes facilitates the uptake of the drug because ultrasound cavitation results in opening of transient pores in cell membrane via a process named sonoporation. Herein, MB-LipoDOX complex was engineered to optimize the size of the complex as well as the loaded DOX content. For this purpose, determination of incubation temperature and time for DOX loading into liposome and optimization of liposome formulation for maximum DOX loading were studied. Ratios of Lipid/Cholesterol/PEGylated lipid, PEG chain length and PEG molar ratio in liposome were determined. Also, determination of Strept Avidin (StAv) to Biotin ratio in LipoDOX and the amount of LipoDOX in LipoDOX-MB complex were studied. For characterization, Dynamic Light Scattering (DLS) method, Fluorescence Spectrometry method and Coulter Counter device were used. Lipoosme size was found to be associated with the pore size of polycarbonate membrane (200nm) resulting in liposomes at around 190±5 nm in size . When the PEGylated lipid with PEG chain of 2000 was used in liposome structure, particle size distribution is more monodispersed than the others. The maximum amount of DOX loaded liposomes was obtained at 32% Cholesterol, 5% DSPE-PEG2000, after 90 min. incubation at 65oC incubation. Optimum StAv to Biotin ratio in LipoDOX was determined as 1.0. The optimum molar ratio of Biotinylated lipids in LipoDOX was determined as 0.05% and the optimum molar ratio of Biotinylated lipids in MBs was determined as 8%.
  • Master Thesis
    Investigation of Shell Microstructure of Microbubbles for Diagnostic Ultrasound
    (Izmir Institute of Technology, 2013) Köse, Derya; Kılıç Özdemir, Sevgi; Kılıç Özdemir, Sevgi
    In this study we reported the effect of shear stress, protein adhesion, temperature, secondary interactions and gas core on microbubble stability which are the main reasons of microbubble dissolution in body. Air filled DSPC/PEG40St microbubbles were examined under shear stress. Increasing PEG40St molar ratio increased the resistivity microbubbles against shear stress. To investigate effect of emulsifier type, microbubbles were produced by mixing DSPC with DSPE-PEG1000, DSPE-PEG2000 and PEG40St at 5:5 molar ratio and PEG40St microbubbles were more stable since it provide better curvature to microbubble shell due to its shape. Shear stress experiments were also performed at different temperatures. With increasing temperature microbubbles became less stable since van der Waals interactions between shell components decreased. When microbubbles were filled with perfluorocarbon, since its solubility is lower and more hydrophobic than air, the stability of microbubbles against shear stress increased. Protein adhesion to microbubble shell was investigated by Langmuir Blodgett (LB) and Surface Plasmon Resonance techniques. Both techniques showed that, as the PEG40St molar ratio and packing density increased, protein adhesion decreased. Secondary interactions between shell components were examined via LB technique and visualized via Brewster Angle Microscopy. As third component to DSPC/PEG40St mixture, StGly, StNH2, DSPS, DSTAP was added and ternary mixtures were generally miscible. Since StGly and StNH2 has single tail, they cannot provide curvature in bubble surface. DSPS and DSTAP mixtures may be recommended drug delivery.
  • Master Thesis
    Design and Characterization of Shell Structure of Microbubbles Used in Ultrasound Imaging
    (Izmir Institute of Technology, 2012) Bölükçü, Elif Şeniz; Kılıç Özdemir, Sevgi
    The main goal of the study is to redesign the microbubble (MB) shell structure and investigate the interactions between the shell components in the mixed monolayers treated as a model for MBs’ shell in order to improve the stability. To examine effects of emulsifier type (DSPC/PEG40 St, DSPC/DSPE-PEGn) and additional components (DSPC/PEG40 St/DSPG, DSPC/PEG40 St/DSPA, DSPC/PEG40 St/DSPE) on stability, molecular interactions and morphological properties, mixtures having various compositions were investigated by Langmuir Blodgett (LB) method and Atomic Force Microscope (AFM) and Brewster Angle Microscope (BAM). For DSPC/PEG40 St monolayers thermodynamically analysis indicated that the attractive forces between the components in the monolayer of 30% PEG40 St were very strong. It was observed that addition of large amount of peg-grafted phospholipids (lipopolymer) increased the attractive forces between molecules in DSPC/DSPE-PEG1000 and DSPC/DSPE-PEG350 monolayers unlike DSPC/DSPE-PEG2000 monolayers. Additionally, the use of different phospholipid as an additional component such as DSPG, DSPE and DSPA in DSPC/PEG40 St mixture signified that intermolecular forces were influenced by the monolayers’ compositions and polar headgroups differences. It was noticed that among the ternary mixtures consisting 70% DSPC, DSPC/PEG40 St/DSPE monolayers exhibited stronger molecular interaction than DSPC/PEG40 St/DSPG and DSPC/PEG40 St/DSPA monolayers while DSPC/PEG40 St/DSPA mixtures showed stronger interaction for mixtures composed of 50% PEG40 St. However, phase separations detected at some regions for these monolayers by BAM and AFM may affect the stability negatively. Therefore, thermodynamically analysis, BAM and AFM results should be evaluated together to assess potential MBs’ shell structures.
  • Master Thesis
    Towards the Design of Ultrasound Contrast Agents: Investigation of Monolayer Microstructure
    (Izmir Institute of Technology, 2011) Akıncı, Saliha Zeyneb; Kılıç Özdemir, Sevgi
    This thesis work is focused on the monolayer formation of phospholipid molecules and surfactants by Langmuir-Blodgett thin film technique on air/water or phosphate buffer interfaces. This study is also devoted to find out the effect of surfactants, the mixing ratio of the components, and also the phosphate buffer solutions on the monolayer films. The pH of the phosphate buffer solution that is used in experiments, is 7.2 and is coherent with the human blood plasma. In addition to this technique, a microscopic technique is employed. The monolayer features in different liquid interfaces are investigated by Brewster angle microscopy technique. In this study, the effect of ionic strength coming from the buffer solutions are examined in whole pure components and mixtures. It is aimed to find out to obtain more detailed information from the surface-pressure versus mean molecular area isotherms that are obtained from Langmuir-Blodgett technique. Therefore, the exact behavior of these organic thin films at the air/liquid interfaces are studied. The miscibility behavior and thermodynamic analysis of the mixed monolayers are also examined for each of the mixtures.