Materials Science and Engineering / Malzeme Bilimi ve Mühendisliği
Permanent URI for this collectionhttps://hdl.handle.net/11147/4719
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Article Citation - WoS: 13Citation - Scopus: 14Synthesis of Albumin Nanoparticles in a Water-Miscible Ionic Liquid System, and Their Applications for Chlorambucil Delivery To Cancer Cells(Elsevier, 2022) Akdoğan, Yaşar; Sözer, Sümeyra Çiğdem; Akyol, Cansu; Başol, Merve; Karakoyun, Çiğdem; Çakan Akdoğan, GülçinSerum albumin has been a preferred protein to generate biodegradable and non-toxic nanoparticles (NPs) for drug delivery applications. Different methods applied for the preparation of serum albumin NPs mostly used organic solvents. Here, we prepared serum albumin NPs in an ionic liquid (IL) system. ILs are considered to be green and designer solvents with unique properties that can replace organic solvents in the synthesis of albumin NPs. Bovine serum albumin (BSA) proteins dissolved in water were transformed into BSA NPs in a water/ Triton™X (TX-100), 1-butanol/1-butyl-3-methylimidazolium trifluoromethanesulfonate (BmimCF3SO3) microemulsion-like system by using a high-speed homogenizer and crosslinker glutaraldehyde. The obtained BSA NPs have been used in drug loading and release studies with a hydrophobic anticancer drug chlorambucil (Chl). Drug loading increased as increasing the ratio of Chl incubated with BSA NPs. Monitoring the drug release by UV–Vis spectroscopy revealed a burst release at first 4 h, but two-thirds of drugs stayed with NPs upon diffusion method. On the other hand, cellular uptake of Chl loaded BSA NPs caused a significant MCF7 breast cancer cell death, whereas free Chl and unloaded BSA NPs did not have a significant effect on the cell viability. Furthermore, in vivo toxicity assessment of BSA NPs obtained in the IL system was conducted in the zebrafish animal model. It showed that zebrafish body is able to eliminate BSA NPs without any toxic side effects and encapsulation of Chl into NPs reduced the toxicity of free Chl. In summary, we showed that BSA NPs with size smaller than 200 nm could be prepared in BmimCF3SO3 mediated system. They can be used for Chl loading (up to 6.9 wt%) with a sustainable release and they induce significant cell death in Chl sensitive cancer cells up to 45% in 24 h. These results indicate that BSA NPs could be prepared alternatively in IL systems and used in drug delivery studies.Article Citation - WoS: 5Citation - Scopus: 4Characterization of Water Solubility and Binding of Spin Labeled Drugs in the Presence of Albumin Nanoparticles and Proteins by Electron Paramagnetic Resonance Spectroscopy(Wiley-Blackwell, 2022) Sözer, Sümeyra Çiğdem; Akdoğan, YaşarElectron paramagnetic resonance (EPR) spectroscopy is an advantageous technique to monitor solubility of drugs in an aqueous solution. In the presence of a drug carrier, the bound and unbound drug fractions can be determined in the same sample simultaneously. To enhance the solubility of hydrophobic drugs, a transporter protein of bovine serum albumin (BSA) can be used directly or in the form of nanoparticle. Moreover, a cationic BSA can be used to enhance anionic drug loading. Here, drugs with different water solubility, salicylic acid (high), ibuprofen (low) and chlorambucil (none) were spin labeled and studied with EPR spectroscopy. Remarkably, it has been shown that albumin nanoparticles are much more effective than albumin proteins in dissolving hydrophobic drugs in water. Furthermore, different drug loading methods were compared, and different from other techniques drug release can be monitored directly from the NPs pellet dissolution by EPR spectroscopy.Article Citation - WoS: 33Citation - Scopus: 40Preparation of Albumin Nanoparticles in Water-In Liquid Microemulsions(Elsevier Ltd., 2019) Demirkurt, Begüm; Çakan Akdoğan, Gülçin; Akdoğan, YaşarIonic liquids (Its) with a variety of properties have been considered a unique class of solvents. Using ILs in microemulsions as oil substitutes provides environmentally benign media for various applications including nanoparticle synthesis. Here, bovine serum albumin nanoparticles (BSA NPs) widely used in drug delivery studies were prepared in nano-sized water droplets of water-in-IL (W/IL) microemulsion systems. A hydrophobic IL of 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF(6)) was used as oil component in place of oils (castor oil, olive oil, etc.) and/or conventional organic solvents (cyclohexane, dichloromethane, etc.) in an emulsification method. In order to obtain spherical BSA NPs, high speed homogenizer treatment was applied followed by glutaraldehyde addition. Effects of glutaraldehyde, speed of homogenizer, type of surfactants and compositional fractions of the microemulsion components on the formation of water droplets and/or preparation of BSA NPs were studied using FTIR, EPR, DLS, and SEM techniques. Optimization of these preparation parameters showed that 3 wt% of BSA in a water/Tween 20/BmimPF(6) microemulsion with 20:50:30 wt% yielded similar to 100 nm average sized BSA NPs based on the SEM analysis. Although, water droplet size strongly depends on the water content, BSA nanoparticle size did not show a significant dependency on the water content. On the other hand, surfactant/IL weight ratio is more crucial for obtaining more uniformly size distributed albumin nanoparticles. A significant cellular uptake of BSA NPs prepared in IL based microemulsions with high cell viability showed the potential of this technique in preparation of albumin nanoparticles that can be used also in drug delivery studies. (C) 2019 Elsevier B.V. All rights reserved.Article Citation - WoS: 17Citation - Scopus: 18Development of an Ionic Liquid Based Method for the Preparation of Albumin Nanoparticles(John Wiley and Sons Inc., 2018) Demirkurt, Begüm; Akdoğan, YaşarAlbumin based nanocarriers have been widely used in drug delivery studies. Here, we developed a water-in-ionic liquid (IL) emulsion-like method to prepare bovine serum albumin (BSA) nanoparticles as alternative to the traditional organic solvents containing techniques. Conformational changes of albumin induced by the imidazolium based ILs at the water-IL interface triggers the BSA nanoparticle formation. The albumin nanoparticle formation are dependent on the experimental parameters and the hydophobicity of the IL. At pH 9.0, using 1.3%wt of BSA in water/1-butyl-3-methyl imidazolium tetrafluoroborate (BmimBF4) (50/50 mol%) and TX-100/butanol surfactant mixture yields uniformly distributed 200 nm average sized BSA nanoparticles. Different than BmimBF4, using a more hydrophilic IL, EmimBF4 yielded albumin aggregates. Instead, using a more hydrophobic IL, HmimBF4 produced albumin nanoparticles but a non-uniform size distribution was obtained. These results indicate that the ionic liquids called green and designer solvents can be also used to synthesize albumin nanoparticles.