Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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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 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 Numerical and Experimental Investigations on the Zeta Potential of Different Size Mesoporous Silica Nanoparticles With Different Porous Properties(Izmir Institute of Technology, 2020) Yakın, Fetiye Esin; Barışık, MuratMesoporous silica nanoparticles (MSN) are utilized by many applications due to their high surface to volume ratio, tunable pore size, low toxicology, and colloidal stability. These properties make silica nanoparticles good candidates for targeted drug delivery applications. Targeted drug delivery steps include cellular internalization, endosomal escape, and cargo release to the selective tissue. The geometric properties of MSN such as particle size, pore size, and porosity, as well as surface chemistry and resulting surface charge density determine the MSN behavior in these steps. This study examines the influence of particle size, pore size, and porosity of an MSN to its surface zeta potential. We performed both numerical and experimental investigations. The zeta potential of various MSNs at different salt concentrations was calculated by solving the Poisson-Nernst-Planck equation with active surface charge boundary conditions considering surface chemistry. We validated our multi-ion model through experiments. Results indicate that zeta potential exhibits a strong dependence on particle size, pore size, and porosity. By increasing porosity and/or pore size, the absolute average zeta potential decreased up to 25% from the theoretical predictions. Second, zeta potentials of silica particles at different sizes and surface areas were experimentally measured at different salt concentrations. Particles were systematically characterized by measuring particle size using Dynamic Light Scattering (DLS), analyzing chemical properties using Fourier-transform infrared spectroscopy (FTIR), measuring surface area using Brunauer– Emmett–Teller (BET) analysis, and imaging using Scanning Electron Microscopy (SEM). A well-dispersed solution in colloidal stability was obtained by systematically tuning corresponding parameters. The absolute average zeta potential was found to increase with a decrease in particle size, while zeta potential was found to decrease with a decrease in surface area at a constant particle diameter, similar to numerical calculations.Master Thesis Investigations on Surface Electric Charge of Silica Nanoparticles With Different Surface Roughnesses(Izmir Institute of Technology, 2019) Alan, Büşra Öykü; Barışık, MuratSilica nanoparticles have been receiving more attention from diverse research areas recently due to their significant physical properties such as large pore volume and high internal surface area, colloidal stability, high biocompatibility, and tunable pore sizes. These silica nanoparticles are great candidates for drug delivery applications because they can transport a large amount of drugs into selective organs and tissues due to their high surface area and large pore volume. However, there are important drug delivery mechanisms that need to be understood properly such as cellular uptake, endosomal escape, drug loading and release, and crossing physical barriers. Physicochemical properties of nanoparticles (size, shape, surface charge, or surface chemistry) are important for understanding these mechanisms in order to develop successful drug delivery applications. This research investigates how these surface charge properties change with different particle, pore diameters, roughness structure on the nanoparticle surface, and different temperature and solution conditions. Also, we investigate how the surface charging behavior of rough nanoparticles interacts with a flat plate. Rough nanoparticles and their interactions with surfaces theoretical assumptions can be wrong and ionic distribution can show variation locally. In order to calculate ionic distribution and surface charge properties in these systems, proper equations and boundary conditions were employed. The charge regulation model was used as a boundary condition because of the electric double layer overlap effect. Results showed that there was a considerable variation on surface charge properties due to the roughness structure with different roughness and particle sizes and temperature difference.Master Thesis Influence of Ca2+ Ions on Freshly Precipitated Caco3 Particles(Izmir Institute of Technology, 2019) Majekodunmi, Olukayode Titus; Özdemir, EkremThe objective of this study was to develop a method to synthesize CaCO3 nanoparticles from a chemical precipitation reaction under ambient and high supersaturation conditions. Equimolar CaCl2 and Na2CO3 solutions were reacted in a tubular reactor at a constant rate. The particles growth inhibition was attempted by dispersing the reaction mixture in a continuously stirred Ca(OH)2 solution. This procedure separated the nucleation phase from the growth inhibition process, and was conducted without pH and composition control. The possibility of impeding the CaCO3 particles overgrowth was explored at different precipitants and Ca(OH)2 concentrations. Their effects on the particles morphology, colloidal stability and specific surface area were studied. Although rapidlysettling particles were produced at precipitants concentration of 100 mM, colloidally stable CaCO3 nanoparticles were obtained at concentrations ≤75 mM. Additive Ca2+ ions, provided by the Ca(OH)2 solutions, inhibited the crystals growth by adsorbing irreversibly on the growth sites. The synthesized particles were as much as 95% smaller than those obtained when pure H2O was used instead. Ca2+ ions concentration and amount of precipitated particles were observed to be important factors for monodispersity and high growth inhibition. Monodisperse and stable nanoparticles were synthesized at low reactants concentration and/or precipitates volume. Vaterite phase was observed in the particles obtained when pure H2O was used as the growth-inhibiting solution. However, the presence of additive Ca2+ ions effected the crystallization of pure calcite, regardless of Ca(OH)2 or precipitants concentration, reaction mixtures retention time in the tubular reactor, volume of precipitates, and the growth-inhibiting solutions initial pH.Master Thesis Design of Micelle Embedded Chitosan Nanocomposites for Targeted Delivery of Hydrophobic Drugs(Izmir Institute of Technology, 2016) Cihan, Esra; Polat, HürriyetWhen successed to synthesize in a nanoparticulate form, chitosan has found to be a very effective biomaterial for drug delivery purposes owing to its extremely attractive characteristics such as its positive charge and pH sensitivity in aqueous medium. However, its structure as it is, is not suitable for oil soluble drugs. Even a close control on the size and shape of chitosan particles alone becomes a state of art and the production of chitosan nanoparticles is very difficult. Therefore, in this study, several methods were designed and used for synthesis of chitosan nanoparticles (<100 nm) with a hydrophobic core that are suitable for oil soluble drugs. Characterization of these nanoparticles were done by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM), Scanning Transmission Microscope (STEM), Transmission Electron Microscope (TEM), surface tension and zeta potential measurements. It was concluded that the best method was the coupling of drug loading with simple ionic gelation method among all the others. Hydrophobic drug loaded micelle embedded chitosan nano particles were able to manufactured successfully. The sizes of chitosan particles that embed Pluronic-123 micelles were larger (<100 nm) than the sizes of Pluronic-123 micelles (20 nm) alone. It was also possible to obtain smaller chitosan nanoparticles (<50 nm) that embed drug loaded Pluronic-123 micelles when their structure is modified by Sodiumdodecylsulfate.Master Thesis Immobilization of Thermophilic Esterase on Magnetic Cornstarch Nanoparticles for Biological Applications(Izmir Institute of Technology, 2016) Öz, Yasin; Şanlı Mohamed, GülşahIn last three decades, even the role of enzymes for biological and industrial applications has become more worthy, enzymes also have some defects. The enzyme immobilization allows to overcome these defects by improving abilities of reusing of catalysts by multiple times, easier reactor operation and product separation. Due to its potential use in biological and industrial applications, isolated thermophilic esterase from Geobacillus sp. was immobilized on magnetic cornstarch nanoparticles. In order to determine activity performance of immobilized enzyme, the effects of temperature, pH and some chemicals on enzyme activity were investigated. The results have shown that after immobilization, the relative activity of immobilized esterase has increased to 80% at 80 0C in comparison to free esterase. Therewithal, the reusability of immobilized esterase has increased fourfold in comparison to free esterase. The magnetic character of the support media has brought ease to separate biocatalysts from reaction media.Master Thesis Chitosan-Plasmid Dna Nanoparticles: Cytotoxic and Cytostatic Effects on Human Cell Lines(Izmir Institute of Technology, 2015) Bor, Gizem; Şanlı Mohamed, Gülşah; Demir, Mustafa MuammerAlthough chitosan nanoparticles (CNs) became a promising tool for several biological and medical applications owing to their inherent biocompatibility and biodegrability, studies regarding their effects on cytotoxicity and cytostatic properties still remain insufficient. Therefore, in the present study, we decided to perform comprehensive analysis of the interactions between CNs – pKindling-Red-Mito (pDNA) and different cell line models derived from blood system and human solid tissues cancers. The resulting CNs-pDNA was investigated with regard to their physical-chemical properties, cellular uptake and transfection efficiency, cytotoxic and cytostatic properties. The nanoparticles showed high encapsulation efficiency and physical stability even after 2 days for various formulations. Moreover, high gene expression levels were observed already 96 h after transfection. CNs-pDNA treatment, despite the absence of oxidative stress induction, caused cell cycle arrest in G0/G1 phase and as consequence led to premature senescence, which turned out to be both, p21-dependent and p21-independent. Also, observed DNMT2 upregulation may suggest the activation of different pathways protecting from the resulting CNs-mediated stress. In conclusion, treatment of different cell lines with CNs-pDNA showed that their biocompatibility was limited and effects were cell type-dependent.Master Thesis Immobilization of Olive Leaf Extract on Chitosan Nanoparticles and Investigation of Their Effects on Cancer Cell Lines(Izmir Institute of Technology, 2014) Özdamar, Burcu; Şanlı Mohamed, GülşahCancer incidence and mortality rates are increasing worldwide in both economically developed and developing countries. Breast cancer in females and lung cancer in males are the most common cancer types. Epidemiological research has provided increasing evidence that dietary habits, especially Mediterranean diet which has high consumption of olive oil and its products, may play an important role in lung and breast cancer. Due to their preventive effect against cancer, olive leaf extract rich in polyphenols was immobilizied on chitosan nanoparticles which are good drug carriers because of their biocompatible and biodegradable properties with the help of capability of passing through biological barriers. For this aim, olive leaf extract loaded chitosan nanaoparticles were synthesized by ionotropic gelation mechanism. Optimum conditions to synthesize nanoparticles were determined by investigation of the effect of chitosan and tripolyphosphate mass ratio, initial pH of chitosan solution, concentration of olive leaf extract and incubation time of olive leaf extract and tripolyphosphate with chitosan solution. Characterization of nanoparticles was performed by dynamic light scattering, atomic force microscopy and infrared spectroscopy. To investigate the anticancer properties of nanoparticles, molecular biological studies were performed by in vitro cytotoxicity studies based on MTT assay, in vitro cell cycle analysis and apoptosis by flow cytometer and imaging of cells by optical microscopy. In results, olive leaf extract loaded chitosan nanaoparticles obtained approximately 91.25 nm and showed more cytotoxicity than chitosan nanoparticles, chitosan and olive leaf extract for both lung and breast cancer cells. In contrast, there was no cytotoxicity for healthy cells. These effects were supported by cell cycle analysis. Also in optical imaging, lower number of cells and morfological differences on cancerous cells which supports the cytotoxicity results were observed. We can conclude that our results will open a new approach to use not only cytotoxic anticancer drug for cancerous cells but also biocompatible material for biomedical applications.Master Thesis Selective Loading of Organofilic Ag Nanoparticles in Ps-Pmma Blends(Izmir Institute of Technology, 2014) Tüzüner, Şeyda; Demir, Mustafa Muammer; Ebil, ÖzgençThe association of nanoparticles with polymer blends offers significant features beyond the advantages of polymer composites prepared by single homopolymer. Since the blends undergo phase separation due to incompatibility of the constituent polymers into various internal structures, the particles can be segregated into one of the phases. Different location of the particles allows to develop novel microstructures; and thus, control over physical properties. In this study, Ag nanoparticles were prepared by reduction of AgNO3 via NaBH4. The particles were capped by cetyl ammonium bromide (CTAB) and were mixed with equimass blend of polystyrene (PS) and poly(methyl methacrylate) (PMMA) in tetrahydrofurane (THF). The solid content of blend solution was fixed at 2.5% w/v. The concentration of the particles with respect to polymer blend was at 0.7 wt %. The composite film was cast on glass slide. Surface feature of the composite films was examined by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The surface of blend film without particles shows spherical pits with a size of 4.5 μm and rich in terms of PMMA. When particle size was small (diameter is around 20 nm), they preferentially located at the interface of the domains. The large particles with a diameter of 90 nm were found to locate in PMMA phase. Upon annealing of the composite film at 165 ˚C for 3 days, the particles move to the PS domains independent of the particle size and merely PS loaded composite is achieved.
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