Master Degree / Yüksek Lisans Tezleri

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

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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, 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%.
  • Master Thesis
    Development of Endosome Disruptive Peptide and Peg Conjugate Based Doxorubicin Delivery System
    (Izmir Institute of Technology, 2019) Özkıyıcı, Selin; Top, Ayben; Top, Ayben; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    In this study, it was aimed to develop a drug carrier system including a TAT-derived cell penetrating peptide in order to provide fast transport of anticancer drugs from endosomal compartments to nucleus. The drug delivery system, denoted as mPEGpeptide- oxime-DOX, was based on polyethylene glycol, endosome disruptive peptide (G2RQR3QR3G2S), and doxorubicin (DOX) conjugate. Control drug delivery system, lack of the peptide (mPEG-oxime-DOX) was also synthesized to assess the effect of the peptide on the physiochemical and drug release properties of the drug carrier. As the first synthesis step, mPEG-OH was converted to mPEG-aldehyde form using DMSO-acetic anhydride oxidation reaction and aldehyde functionalization was determined by using FTIR and NMR spectroscopy. The peptide and mPEG-peptide were synthesized using solid phase synthesis protocol, and their purities were confirmed using HPLC and MALDI-TOF mass spectroscopy analyses. Prior to DOX conjugation, hydroxyl group of serine residue in the mPEG-peptide system was oxidized to aldehyde. The anticancer drug was attached to the carrier molecules via amine-aldehyde reaction forming an acid cleavable oxime bond. Drug release, size distribution, and stability of the PEG-peptideoxime- DOX system were evaluated and compared with those results of the control drug delivery system. For mPEG-oxime-DOX, a pH programmed DOX release with the respective % DOX release values of ~68 % and ~28 % at pH 5.0 and pH 7.4 was observed. For mPEG-peptide-oxime-DOX, on the other hand, quite low DOX release (~10-15 %) was obtained for both pH values suggesting possible interaction between DOX and the peptide. Mean size value of the mPEG-oxime-DOX was measured as ~24 nm. However, mPEG-peptide-oxime-DOX, had quite lower hydrodynamic diameter values (~3nm and ~6 nm at pH 5.0 and pH 7.4, respectively) possibly due to repulsions between the arginines in the peptide domain. Observation of the morphology and evaluation of the cytotoxicity of these drug delivery systems are underway.