Person: TOKSOY ÖNER, EBRU
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TOKSOY ÖNER
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Publication Metadata only Lecithin-acrylamido-2-methylpropane sulfonate based crosslinked phospholipid nanoparticles as drug carrier(WILEY, 2016) TOKSOY ÖNER, EBRU; Mutlu, Esra Cansever; Bostan, Muge Sennaroglu; Bahadori, Fatemeh; Kocyigit, Abdurrahim; Oner, Ebru Toksoy; Eroglu, Mehmet S.In this study, a novel paclitaxel (PTX) loaded and a crosslinked solid phospholipid nanoparticles (SLN-PTX) with negative surface charge was prepared by UV polymerization for drug delivery. Capping of positive charge of zwitterionic lecithin with negative charge of sodium 2-acrylamido-2-methyl-1-propanesulfonate (AMPS-Na) through cation exchange interaction produced a lecithin-AMPS (L-AMPS) complex. The amphiphilic and negative charged lipid complex was emulsified in the presence of emulsifier, paclitaxel, initiator, and methacrylated poly epsilon-caprolacton-diol (PCL-MAC) as a spacer. The colloidal system was subjected to UV-irradiation to obtain crosslinked nanoparticles. Completion of the UV-polymerization was monitored with differential scanning calorimetry (DSC), which indicated the disappearance of exothermic peaks of vinyl groups. The nanoparticle system, having an average size of 200 nm, exhibited high drug encapsulation (96%) with negatively charged surface (zeta potential had an average of -70 mV). PTX release profiles of the crosslinked and uncrosslinked SLN-PTXs were studied and their pharmacological properties were compared. The crosslinked nanoparticles exhibited more controlled release behavior with longer release time compared to the uncrosslinked ones. In vitro cytotoxicity test was conducted on MCF-7 human breast adenocarcinoma cell line, which indicated that the crosslinked SLN-PTXs have a potential therapeutic effect for breast cancer treatments. (c) 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44105.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 Levan Nanostructured Thin Films by MAPLE Assembling(AMER CHEMICAL SOC, 2011) TOKSOY ÖNER, EBRU; Sima, Felix; Mutlu, Esra Cansever; Eroglu, Mehmet S.; Sima, Livia E.; Serban, Natalia; Ristoscu, Carmen; Petrescu, Stefana M.; Oner, Ebni Toksoy; Mihailescu, Ion N.Synthesis of nanostructured thin films of pure and oxidized levan exopolysaccharide by matrix-assisted pulsed laser evaporation is reported. Solutions of pure exopolysaccharides in dimethyl sulfoxide were frozen in liquid nitrogen to obtain solid cryogenic pellets that have been used as targets in pulsed laser evaporation experiments with a KrF* excimer source. The expulsed material was collected and assembled onto glass slides and Si wafers. The contact angle studies evidenced a higher hydrophilic behavior in the case of oxidized levan structures because of the presence of acidic aldehyde hydrogen bonds of the coating formed after oxidation. The obtained films preserved the base material composition as confirmed by Fourier transform infrared spectroscopy. They were compact with high specific surface areas, as demonstrated by scanning electron and atomic force microscopy investigations. In vitro colorimetric assays revealed a high potential for cell proliferation for all coatings with certain predominance for oxidized levan.Publication Metadata only Sugar Based Biopolymers in Nanomedicine; New Emerging Era for Cancer Imaging and Therapy(BENTHAM SCIENCE PUBL LTD, 2017) TOKSOY ÖNER, EBRU; Eroglu, Mehmet S.; Oner, Ebru Toksoy; Mutlu, Esra Cansever; Bostan, Muge SennarogluSince last decade, sugar based biopolymers are recognized in nanomedicine as promising materials for cancer imaging and therapy. Their durable, biocompatible and adhesive properties enable the fine tuning of their molecular weights (MW) and their miscellaneous nature makes the molecules acquire various conformations. These in turn provide effective endocytosis by cancer cell membranes that have already been programmed for internalization of different kinds of sugars. Therefore, biocompatible sugar based nanoparticles (SBNPs) are suitable for both cell-selective delivery of drugs and imaging through the human body. Recently, well known sugar-based markers have displayed superior performance to overcome tumor metastasis. Thereby, targeting strategies for cancer cells have been broadened to sugar-based markers as noticed in various clinic phases. In these studies, biopolymers such as chitosan, hyaluronic acid, mannan, dextran, levan, pectin, cyclodextrin, chondroitin sulphate, alginates, amylose and heparin are chemically functionalized and structurally designed as new biocompatible nanoparticles (NPs). The future cancer treatment strategies will mainly comprise of these multifunctional sugar based nanoparticles which combine the therapeutic agents with imaging technologies with the aim of rapid monitoring response to therapies. While each individual imaging and treatment step requires a long time period in effective treatment of diseases, these multifunctional sugar based nanoparticles will have the advantage of rapid detection, right drug efficiency evaluation and immediate interfere opportunity to some important diseases, especially rapidly progressing cancers. In this article, we evaluated synthesis, characterization and applications of main sugar based biopolymers and discussed their great promise in nano-formulations for cancer imaging and therapy. However much should be done and optimized prior to clinical applications of these nano-formulations for an efficient drug treatment without overall toxicity for getting most effective clinical results.Publication Metadata only Sulfated Halomonas levan as a heparin-mimetic bioactive glycan(ELSEVIER SCIENCE BV, 2016) TOKSOY ÖNER, EBRU; Erginer, Merve; Coskunkan, Binnaz; Morova, Tunc; Rende, Deniz; Bucak, Seyda; Baysal, Nihat; Ozisik, Rahmi; Eroglu, Mehmet S.; Agirbasli, Mehmet; Oner, Ebru ToksoyPublication 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-based hydrogels for controlled release of Amphotericin B for dermal local antifungal therapy of Candidiasis(ELSEVIER, 2020) TOKSOY ÖNER, EBRU; Demirci, Tuba; Haskoylu, Merve Erginer; Eroglu, Mehmet Sayip; Hemberger, Jurgen; Oner, Ebru ToksoyHydrogels from Halomonas levan polysaccharide were prepared at different crosslinking densities. Swelling results demonstrated pH dependent rather than temperature dependent swelling of the hydrogel and the highest swelling value was achieved at basic conditions with a swelling ratio of 9.1 +/- 0.1 which is the highest reported for levan based hydrogels. SEM images show a porous network architecture, which indicates a large surface area of the hydrogels. Rheological analyses showed the viscoelastic behavior of the hydrogels. Biocompatibility of the hydrogels was confirmed by cell culture experiments. For drug release experiments Amphotericin B (AmB) was used. 51% of the loaded AmB was released into the PBS buffer and the released AmB had a significant antifungal activity against Candida albicans.