Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Development of Ultrasound Triggered Drug Delivery Systems for Cancer Treatment(Izmir Institute of Technology, 2019) Önercan, Cansu; Kılıç Özdemir, SevgiDoxorubicin (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 Development of Drug-Loaded Microbubbles for In-Vitro Applications in Cell Biology(Izmir Institute of Technology, 2017) Coşkun, Sema; Özdemir, Ekrem; Sultan Altun, ZekiyeDoxorubicin (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.