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.Liposomes

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Now showing 1 - 3 of 3
  • 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
    Development of Ultrasound Triggered Drug Delivery Systems for Cancer Treatment
    (Izmir Institute of Technology, 2019) Önercan, Cansu; Kılıç Özdemir, Sevgi; Kılıç Özdemir, Sevgi; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    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%.