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, SevgiSubject: search.filters.subject.Microbubbles

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Now showing 1 - 3 of 3
  • 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.