Person: TOKSOY ÖNER, EBRU
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TOKSOY ÖNER
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Publication Metadata only Sulfated levan from Halomonas smyrnensis as a bioactive, heparin-mimetic glycan for cardiac tissue engineering applications(ELSEVIER SCI LTD, 2016) TOKSOY ÖNER, EBRU; Erginer, Merve; Akcay, Ayca; Coskunkan, Binnaz; Morova, Tunc; Rende, Deniz; Bucak, Seyda; Baysal, Nihat; Ozisik, Rahmi; Eroglu, Mehmet S.; Agirbasli, Mehmet; Oner, Ebru ToksoyChemical derivatives of levan from Halomonas smyrnensis AAD6T with low, medium and high levels of sulfation were synthesized and characterized by FTIR and 2D-NMR. Sulfated levan samples were found to exhibit anticoagulation activity via the intrinsic pathway like heparin in a dose-dependent manner. Exceptionally high heparin equivalent activity of levan sulfate was shown to proceed via thrombin inhibition where decreased Factor Xa activity with increasing concentration was observed in antithrombin tests and above a certain concentration, levan sulfate showed a better inhibitor activity than heparin. In vitro experimental results were then verified in silico by docking studies using equilibrium structures obtained by molecular dynamic simulations and results suggested a sulfation dependent binding mechanism. With its high biocompatibility and heparin mimetic activity, levan sulfate can be considered as a suitable functional biomaterial to design biologically active, functionalized, thin films and engineered smart scaffolds for cardiac tissue engineering applications. (C) 2016 Elsevier Ltd. All rights reserved.Publication Metadata only Comprehensive characterization of chitosan/PEO/levan ternary blend films(ELSEVIER SCI LTD, 2014) TOKSOY ÖNER, EBRU; Bostan, Muge Sennaroglu; Mutlu, Esra Cansever; Kazak, Hande; Keskin, S. Sinan; Oner, Ebru Toksoy; Eroglu, Mehmet S.Ternary blend films of chitosan, PEO (300,000) and levan were prepared by solution casting method and their phase behavior, miscibility, thermal and mechanical properties as well as their surface energy and morphology were characterized by different techniques. FT-IR analyses of blend films indicated intermolecular hydrogen bonding between blend components. Thermal and XRD analysis showed that chitosan and levan suppressed the crystallinity of PEO up to nearly 25% of PEO content in the blend, which resulted in more amorphous film structures at higher PEO/(chitosan + levan) ratios. At more than 30% of PEO concentration, contact angle (CA) measurements showed a surface enrichment of PEO whereas at lower PEO concentrations, chitosan and levan were enriched on the surfaces leading to more amorphous and homogenous surfaces. This result was further confirmed by atomic force microscopy (AFM) images. Cell proliferation and viability assay established the high biocompatibility of the blend films. (C) 2013 Elsevier Ltd. All rights reserved.Publication Metadata only Development and optimization of a novel PLGA-Levan based drug delivery system for curcumin, using a quality-by-design approach(ELSEVIER, 2019) TOKSOY ÖNER, EBRU; Bahadori, Fatemeh; Eskandari, Zahra; Ebrahimi, Nabiallah; Bostan, Muge Sennaroglu; Eroglu, Mehmet Sayip; Oner, Ebru ToksoyThis study aimed to develop a PLGA, Levan-based drug delivery system (DDS) of Curcumin using a quality-by-design (QbD) approach to reveal how formulation parameters affect the critical quality attributes (CQAs) of this DDS and to present an optimal design. First, a risk assessment was conducted to determine the impact of various process parameters on the CQAs of the DDS (i.e., average particle size, ZP, encapsulation efficiency and polydispersity index). Plackett-Burman design revealed that potential risk factors were Levan molecular weight, PLGA amount and acetone amount. Then, the optimization of the DDS was achieved through a Box-Behnken Design. The optimum formulation was prepared using low molecular weight Levan (134 kDa), 51.51 mg PLGA and 10 ml acetone. The model was validated and the optimized formulation was further characterized using different physic-chemical methods. The study resulted in the most stable NP with a spherical and uniform shape and physical stability tests indicated its stability for at least 60 days at room temperature. In conclusion, this study was an effort for developing a DDS which solubilizes Curcumin in clinically applicable concentrations.Publication Metadata only Halomonas smyrnensis as a cell factory for co-production of PHB and levan(ELSEVIER SCIENCE BV, 2018) KASAVİ, CEYDA; Tohme, Souha; Haciosmanoglu, Gul Gulenay; Eroglu, Mehmet Sayip; Kasavi, Ceyda; Genc, Seval; Can, Zehra Semra; Oner, Ebru ToksoyLevan is a fructan type polysaccharide that has long been considered as an industrially important biopolymer however its limited availability is mainly due to the bottlenecks associated with its large-scale production. To overcome such bottlenecks in the commercialization of this very promising polysaccharide, co-production of levan with polyhydroxyalkanoates (PHAs) by halophilic Halomonas smyrnensis cultures has been proposed in this study for the first time. After in silico and in vitro assessment of PHA accumulation, fermentation profiles for levan and PHA concentrations were obtained in the presence of sucrose and glucose and the PHA granules observed by TEM were found to be poly(3-hydroxybutyrate) (PHB) after detailed structural characterization by GC-MS, DSC, FTIR and NMR. Six nutrient limitation strategies based on nitrogen (N) and phosphorus (P) were tested but highest levan and PHB yields were obtained under unlimited conditions. H. smyrnensis is proved to co-produce PHB and levan while using inexpensive carbon sources which is a commercially successful microbial cell factory system showing a great potential in lowering manufacturing costs and aiming for a zero waste policy within the biorefinery concept. (C) 2018 Elsevier B.V. All rights reserved.Publication Metadata only Novel levan and pNIPA temperature sensitive hydrogels for 5-ASA controlled release(ELSEVIER SCI LTD, 2017) TOKSOY ÖNER, EBRU; Osman, Asila; Oner, Ebru Toksoy; Eroglu, Mehmet S.Levan based cross-linker was successfully synthesized and used to prepare a series of more biocompatible and temperature responsive levan/N-isopropyl acrylamide (levan/pNIPA) hydrogels by redox polymerization at room temperature. Volume phase transition temperature (VPTT) of the hydrogels were precisely determined by derivative differential scanning calorimetry (DDSC). Incorporation of levan into the pNIPA hydrogel increased the VPTT from 32.8 degrees C to 35.09 degrees C, approaching to body temperature. Swelling behavior and 5-aminosalicylic acid (5-ASA) release of the hydrogels were found to vary significantly with temperature and composition. Moreover, a remarkable increase in thermal stability of levan within hydrogel with increase of pNIPA content was recorded. The biocompatibility of the hydrogels were tested against mouse fibroblast L929 cell line in phosphate buffer saline (PBS, pH 7.4). The hydrogels showed increasing biocompatibility with increasing Levan ratio, indicating levan enhanced the hydrogel surface during swelling. (C) 2017 Elsevier Ltd. All rights reserved.Publication Metadata only Levan enhanced the NF-kappa B suppression activity of an oral nano PLGA-curcumin formulation in breast cancer treatment(ELSEVIER, 2021) TOKSOY ÖNER, EBRU; Eskandari, Zahra; Bahadori, Fatemeh; Yenigun, Vildan Betul; Demiray, Mutlu; Eroglu, Mehmet Sayip; Kocyigit, Abdurrahim; Oner, Ebru ToksoyChemoresistance (CR) is one of the reasons why chemotherapy agents like Gemcitabine (GMC) remain insufficient in healing breast cancer. Activation of Nuclear Factor-kappa B (NF-kappa B) during chemotherapy is known as an important factor in the development of CR. The hydrophobic polyphenol curcumin is shown to inhibit NF-kappa B and hence CR. The aim of this work was to increase the poor bioavailability of curcumin by loading it into the nano-micelles made of Poly (Lactide-co-Glycolide) (PLGA) and levan, where levan as a natural fructose homopolymer makes the nano-micelle more stable and increases its uptake using the fructose moieties. In this study, a PLGA-levan-curcumin formulation (PLC) was designed and characterized. The size was measured as 154.16 +/- 1.45 nm with a 67.68% encapsulation efficiency (EE%). The incorporation between the components was approved. Levan made the nano-micelles stable for at least three months, increased their uptake, and led to a 10,000-fold increase in the solubility of curcumin. The enhanced bioavailability of curcumin reduced the NF-kappa B levels elevated by GMC, both in vitro and in vivo. The PLC showed a complete tumor treatment, while GMC only showed a rate of 52%. These point to the great potential of the PLC to be used simultaneously with chemotherapy.