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, Umut
    Serum 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, Yaşar
    Nanoparticles (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 Muammer
    The 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.