Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Synthesis of Drug Loaded Ph Sensitive Albumin Nanoparticles(2023) Argıtekin, Eda; Akdoğan, Yaşar; Adem, UmutSerum albumin-based nanoparticles (NPs) are commonly used for drug delivery due to their stability, biodegradability, ease of particle size control and no toxicity. In this study, bovine serum albumin (BSA) was functionalized with catechol-containing dopamine (D) to synthesize D-BSA NPs using pH responsive catechol-metal coordination bonds. Instead of using glutaraldehyde, V(III) ion was used as a cross-linker for synthesizing NPs. Catechol-V(III) coordination bonds provided pH responsive NPs due to their different stoichiometry of catechol-metal complexes (e.g. mono-, bis- or tris-) at different pH values. For the synthesis of D-BSA NPs, desolvation method was used with acetone as desolvating agent. Uniformly sized NPs were synthesized with an average of 294 nm with a PDI value of 0.15. Doxorubicin is loaded to NPs with a 15:1 DOX:D-BSA molar ratio. DOX encapsulation efficiency and drug loading capacity of D-BSA NPs were found to be 98% and 10%, respectively. Conversion to bis- and/or mono- catechol-V(III) complexes in acidic medium resulted in degradation of NPs and rapid release of the loaded doxorubicin (DOX). DOX releases reached to 51, 76 and 95% at pH values 7.4, 5.5 and 4.2, respectively at the end of 80 hours. Furthermore, the cytotoxic effects of prepared D-BSA NPs, in comparison to free DOX were studied with MCF-7 cells. Increasing D-BSA concentrations up to 0.2 mg/mL did not affect the cell viability, significantly. But, upon cell (MCF-7) uptake in vitro, DOX-loaded D-BSA NPs and free DOX reduced cell viability by 75% and 20% in 24 hours, respectively.Master Thesis Preparation of Drug Loaded Albumin Nanoparticles in Water / Ionic Liquids Microemulsion Systems(Izmir Institute of Technology, 2021) Yıldırım, Barış; Akdoğan, YaşarNanoparticles (NPs) have been used in various applications such as biotechnology, nanomedicine, and drug delivery systems. Many nanoparticle drug delivery systems have been promoted for cancer treatment, and numerous materials have been investigated to use as drug delivery agents to enhance the therapeutic efficiency and safety of anticancer drugs. Albumin is a natural biopolymer and the most abundant protein in blood plasma. Due to its versatile binding capacity of widespread therapeutical drugs, albumin becomes an ideal material to obtain nanoparticles. In this study, the ionic liquid (IL) based emulsification methods were investigated. Instead of classical toxic and volatile solvents, using ILs in microemulsions, environment-friendly media were received to synthesize bovine serum albumin (BSA) NPs. In order to obtain BSA NPs, high-speed homogenizer processing was applied by following crosslinker addition. The IL microemulsions are a thermodynamically stable colloidal dispersion containing spherical droplets (W/IL or IL/W) in submicron sizes that act as nanoreactors for NP formation. Chlorambucil (CHL) was used as a model drug to investigate drug loading and releasing kinetics of BSA NPs as a drug delivery candidate. Results showed that chlorambucil loading capacities and release kinetics depended on the synthesized medium such as anion-type of ILs and surfactants. CHL loaded to the BSA NPs synthesized in hydrophilic IL BmimBF4 in relatively higher amounts and released in the same trend. In addition, the cell viability effect of CHL-loaded BSA NPs synthesized in different types of ILs were investigated. The CHL-loaded BSA NPs synthesized in BmimOTf and BmimPF6 reduced the cancer cell viability more than the used same dose of free CHL.Master Thesis Preparation and Characterization of Drug Loaded Cationic Albumin Nanoparticles(01. Izmir Institute of Technology, 2021) Sözer, Sümeyra Çiğdem; Akdoğan, Yaşar; Emrullahoğlu, MustafaSerum albumin protein behaves as a carrier and transporter for both hydrophilic and hydrophobic drugs. Therefore, albumin could be used in the drug carrier systems. Since albumin nanoparticles have a negative charge under physiological conditions, their anionic drug loading and delivering capacities are restricted. This study aims to obtain higher anionic drug loading capacity by producing cationic bovine serum albumin nanoparticles (cBSA NPs). Firstly, the carboxyl groups of amino acids present on the surface of albumin were conjugated with ethylenediamine to change the charge of albumin from negative to positive. Then, cBSA NPs were obtained using the desolvation process. Anionic salicylic acid (SA) was used for drug loading studies of the obtained cBSA NPs. SA loading and releasing experiments were studied with UV-Vis and electron paramagnetic resonance (EPR) spectroscopy. In the UV-Vis, the drug loading capacity of cBSA NPs was found to increase ~2 fold, and drug release was slower compared to BSA NPs. For EPR studies, SA was labeled with stable radicals. Spin labels allow the simultaneous monitoring of bound and free drugs in the same sample. The drug was loaded into nanoparticles using two methods. Based on EPR results, it was found that drug was loaded to cBSA NPs with 50% and 93%, and to BSA NPs with 4% and 15% ratios, by desolvation and incubation, respectively. Thus, UV-vis and EPR measurements showed that cBSA NPs have higher SA loading potential and slower release ability compared to anionic albumin nanoparticles.Master Thesis Studying Dopa Adhesion on Polystyrene Under Water(Izmir Institute of Technology, 2021) Yıldız, Remziye; Akdoğan, Yaşar; Emrullahoğlu, MustafaMussels wet adhesive performance has been arousing curiosity for a long time. It is found that 3,4-dihydroxyphenylalanine (DOPA) is responsible for adhesive properties of mussels. Despite a large body of research characterizing the interactions DOPA with hydrophilic surfaces, relatively few works have addressed the mechanism of interactions with hydrophobic surfaces. The benzene ring of DOPA is the main attributor to the adhesion on hydrophobic polystyrene (PS) surface. However, here we showed that two hydroxyl groups of catechol have also effects on wet adhesion. We studied wet adhesive properties of DOPA, tyrosine and phenylalanine functionalized PEG polymers, PEG-(N-Boc-L-DOPA)4, PEG-(N-Boc-L-Tyrosine)4, PEG-(N-Boc-L-Phenylalanine)4, on spin labeled PS nanobeads (SL-PS) by electron paramagnetic resonance (EPR) spectroscopy. Surface coverage ratio of SL-PS upon additions of PEG-(N-Boc-L-DOPA)4, PEG-(N-Boc-L-Tyrosine)4 and PEG-(N-Boc-L-Phenylalanine)4 showed that SL-PS was covered with 70%, 50% and 0%, respectively. This showed that spontaneous wet adhesion on PS increases with the number of amino acids hydroxyl groups. This is also supported with the density functional theory (DFT) energy calculations and ab-initio molecular dynamics (AIMD) simulations. In water, interactions between water molecules and hydroxyl groups on the catechol induce catechol adhesion via π-π stacking between the catechol and double styrene rings which were already tilted out with water.Master Thesis Preparation and Characterization of Serum Albumin Nanoparticles Obtained From Modified Bovine Serum Albumin(01. Izmir Institute of Technology, 2021) Özmen Egesoy, Tuğçe; Akdoğan, Yaşar; Demir, Mustafa MuammerThe serum albumin has been used as a drug nanocarrier for a long time due to its rich drug transportation ability. Here, modified bovine serum albumin (BSA) proteins were obtained by conjugation with ethylenediamine and dopamine molecules, separately. Using these modified proteins, new BSA nanoparticles were obtained by a desolvation method. Native BSA has a net negative charge at the physiological condition. However, ethylenediamine conjugation yields a positive charge on it, and thus produces cationic BSA (cBSA) protein. On the other hand, dopamine functionalization (D-BSA) makes BSA eager to coordinate with transition metals. After preparation of modified proteins (cBSA and D-BSA), their nanoparticles were prepared with desolvation method but using different crosslinking mechanisms. For cBSA NPs preparation, a traditional crosslinking agent of glutaraldehyde was used. However, for D-BSA NPs preparation, Fe(III) ions were added to the system to achieve the stable nanoparticle formation. In order to obtain cBSA NPs, several organic solvents were used as desolvating agents. cBSA NPs with an average size around 200 nm were obtained in a high formation yield (54.8%) only through addition of acetonitrile to the cBSA aqueous solution. Similarly, different desolvating agents were studied to obtain D-BSA NPs. The promising results were obtained upon addition of 1:5 (v/v) of water/acetone mixture. After addition of the desolvating agent, Fe(III) ions were added to the solution to interconnect D-BSA with each other. This connection is pH sensitive therefore albumin nanoparticles were stable at basic pH values but not at acidic pH values. By this way, pH sensitive D-BSA NPs around 300 nm particle sizes were obtained.Master Thesis Functionalization and Thickness Dependent Properties of Single Layer Dichalcogenides(Izmir Institute of Technology, 2019) Kahraman, Zeynep; Şahin, Hasan; Akdoğan, YaşarAfter successful isolation of graphene in 2004, it was found that the layered materials showed different properties when diluted to the monolayer. The layer dependent structural, electronic and vibrational properties of the 1T phase of two dimensional (2D) platinum diselenide are investigated by means of state-of-the-art first-principles calculations. In addition ultra-thin two-dimensional Janus type platinum dichalcogenide crystals formed by two different atoms at opposite surfaces are investigated by performing state-of-the-art density functional theory calculations. While all Janus structures are indirect band gap semiconductors as their binary analogs, their Raman spectra show distinctive features that stem from broken out-of-plane symmetry. Moreover, it was shown that vertically stacked van der Waals heterostructures of binary and ternary (Janus) platinum dichalcogenides offer wide-range electronic features by forming bilayer heterojunctions of type-I, type-II and type-III. On the other hands, Ab initio calculations are performed in order to investigate the structural, vibrational, electronic, and piezoelectric properties of both bare TaS2 and its functionalized structures. Furthermore, the elastic and piezoelectric properties of TaS2 and its derivatives are analyzed. It is revealed that the in-plane piezoelectricity of TaS2 can be enhanced via one-surface fluorination while an additional degree of freedom for the piezoelectricity can be added in all Janus structures due to the broken out-of-plane symmetry. This thesis provides some important results understanding of thickness and functionalization dependent mechanics, vibrational, electronic properties of 2D materials.Master Thesis Investigation of Tribological Performance of B4c Reinforced Aluminium Matrix Composites(Izmir Institute of Technology, 2019) Serkir, Sevgi; Kandemir, Sinan; Akdoğan, YaşarAluminium, on account of its easy accessibility and superior metallic characteristics, has a wide variety of applications. Increasing demand on the use of aluminium in areas such as automobile, aviation and space industries which requires high performance has led to development of aluminium metal matrix composites. For this purpose, the ceramic reinforcing particles are mostly preferred to provide better mechanical and tribological properties than their conventional counterparts. In this study, aluminium metal matrix composite (AMC) reinforced with 5 wt.%, 10 wt.% and 15wt.% of B4C were fabricated using the powder metallurgy method. In order to obtain the optimum processing parameters necessary for efficient fabrication, several trials, at first place, were studied under different conditions by changing milling parameters such as milling time, milling medium, milling speed and process control agent, and sintering process parameters such as sintering time, sintering temperature. The production of composite powders was carried out using a planetary ball mill in a wet medium for 7 hours with 0.05 wt.% of stearic acid process control agent which helps to avoid contamination and cold welding of ductile Al particle. The milled powders were pressed at 314 MPa at RT and composite samples with a diameter of 30 mm and a height of 4 mm were obtained. The samples were sintered at 550, 575, 600 and 625ºC for one hour under argon atmosphere. The micro-structures of samples were analysed by scanning electron microscopy and the X-ray diffraction techniques. The wear behaviour of sintered composite samples with ball-on-disc dry wear tester and the mechanical behaviour of the samples with Vickers hardness test were investigated.Master Thesis Obtaining and Characterization of Artificial Leather Using Different Types of Plasticizers(Izmir Institute of Technology, 2019) Akkuş Altındağ, İffet; Akdoğan, Yaşar; Adem, UmutArtificial leather is the material which has wide range of use in life from fashion garment, upholstery to technical applications such as defense industries. PVC artificial leather is preferred material by manufacturers because of its low cost and modification can be done easily by using true plasticizers which are fitting for purpose. In this study, number of six different plasticizers which are non-phthalate plasticizers; trioctyl trimelliate (TOTM), tributyl trimelliate (TBTM), dioctyl terephthalate (DOTP), tributyl citrate (TBC), dioctyl adipate (DOA) and dioctyl succinate (Plast BIO) were used for obtaining artificial leather. To characterize the properties of different kinds of plasticizer in artificial leather, mechanical tests including tensile and tear strengths, elongation at break, cold flexibility and effects of migrability tests were applied. Materials were formulated at three degrees of plasticizers ratios. Also, chemical changes during plasticization were observed using FTIR spectroscopy with ATR accessory, according to types and used levels of plasticizers. In conclusion, plasticizers showed different properties, i.e. material with TOTM plasticized had maximum tear and tensile strengths, while DOA and TBC including materials showed maximum elongation under same load. Considering cold flexibility of six plasticizers, DOA, BIO and TBC have more resistance to cold were obtained, respectively. In addition, migration studies showed that plasticizers including TOTM and TBTM have the least migration properties.Master Thesis Batio3 Based Ferroelectric Materials for Electrocaloric Cooling Applications(Izmir Institute of Technology, 2018) Şanlı, Keriman; Adem, Umut; Akdoğan, YaşarThe aim of this project was to produce electrocaloric materials and to determine the potential of these materials for electrocaloric cooling applications. The electrocaloric effect (ECE) of lead-free Ba0.8Sr0.2Ti1-xZrxO3 (0 ≤ x ≤ 0.10) ferroelectric ceramics was studied. The phase analysis of each ceramic composition that was synthesized by conventional solid-state reaction technique was performed by X-ray Diffraction. Dielectric measurements were done to determine the phase transition temperatures (Curie temperature, Tc) of all compositions and also construct a phase diagram. ΔT values were calculated indirectly using electrical polarization curves measured at different temperatures and Maxwell's equations. ΔT values that were obtained from different regions of the phase diagram are compared. The most suitable composition for applications was chosen considering the ΔT value, temperature range where relatively large ΔT is preserved and the Curie temperature of all ceramics. Ba0.8Sr0.2Ti0.93Zr0.07O3 ceramic located near the critical point shows the best performance with ΔT value of 0.40 K under 20 kV/cm. In comparison with the lead-free ceramics studied in the literature, Ba0.8Sr0.2Ti1-xZrxO3 system can be considered as one of the best candidates for future electrocaloric cooling technologies.Master Thesis Study of Drug Transportation by Esr Spectroscopy(Izmir Institute of Technology, 2018) Tatlıdil, Duygu; Akdoğan, Yaşar; Emrullahoğlu, MustafaThe ability to track drug binding and release makes electron spin resonance (ESR) spectroscopy well suited for drug delivery studies. Using the continuous wave cw ESR technique to extract information about the dynamics of the spin labeled drugs we can simultaneously determine the bound and unbound drugs. In this study, ESR technique was used to detect the binding and release of spinlabeled salicylic acid (SLSA) to and from bovine serum albumin (BSA), and to detect different binding interactions between them. We have labeled salicylic acid with stable nitroxide-based tempo radicals to monitor the BSA bound and unbound conditions of the drug. Studying with the different concentrations of SLSA-BSA binding showed that the drug-protein stoichiometry increases significantly in the physiological range of BSA concentration. Also, during the release of SLSA from BSA, there is an unchanging balance between the bound and unbound SLSA. In order to study various drug binding interactions, SL-benzoic acid, SL-phenol, SL-benzene, SL-cyclohexane, SL-hexane and SL-methyl were prepared. We showed that the main conjugation in the binding of these drugs to BSA is hydrophobic interaction. In addition, cationic BSA (cBSA) was prepared to investigate the effect of electrostatic interaction on drug binding. The SLSA loading capacity of cBSA is significantly higher than that of BSA, this result indicates the importance of electrostatic interactions for the drug binding. Finally, we examined the competitive binding behaviors of salicylic acid, ibuprofen and aspirin to BSA. Binding sites of SL-salicylic acid and SL-ibuprofen in BSA show 96% of similarities. In addition, our results showed that binding sites of SL-salicylic acid and SL-aspirin in BSA have 73% of similarities.These results demonstrate that cw ESR spectroscopy with the spin labeling technique is an effective technique for the determination of drug-protein interactions and stoichiometric analysis of drug binding.