Person: TEKARSLAN ŞAHİN, ŞEYMA HANDE
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Publication In vitro cytotoxic activity of microalgal extracts loaded nano-micro particles produced via electrospraying and microemulsion methods(2019-07-18T00:00:00Z) Karakas, Canan Y.; ERGİNER, Yıldız; Sahin, Hande Tekarslan; ÖZÇİMEN, Didem; Inan, Benan; TEKARSLAN ŞAHİN, ŞEYMA HANDEReactive oxygen species can bind protein, DNA, lipids, and carbohydrates and thus cause an oxidation reaction that induces various syndromes such as cardiovascular diseases, degenerative disease, and cancer types in the human body. Bioactive compounds, such as PUFA, EPA, DHA, and carotenoids in algae, have a chain ring and protect the tissue from chemical damage and reverse the symptoms of some diseases. Algal bioactives also have various biological properties such as anticoagulants, antiviral, antiangiogenic, antitumor, anti-inflammatory, antioxidant, antiproliferative, and immune modulation properties. This study aimed to show in vitro cytotoxic activity effect of Chlorella protothecoides and Nannochloropsis oculata microalgal extracts loaded nano-microparticles on A-172 (Homo sapiens brain glioblastoma) and HCT-116 (H. sapiens colon colorectal carcinoma) cell lines because of the increasing importance of algal biotechnology. MTT viability tests were performed on HUVEC, A172, and HCT 116 cells with particles obtained at optimum process parameters. The cell viability rates of encapsulated particles were also compared with pure algae extracts. Microalgal extracts loaded nano-micro particles showed very promising results for cytotoxic effect on cancer cells.Publication Saccharomyces(2021-05-01T00:00:00Z) Tekarslan Şahin, Şeyma Hande; TEKARSLAN ŞAHİN, ŞEYMA HANDEPublication Applications of cell culture studies in pharmaceutical technology(2017-01-01T00:00:00Z) Tekarslan Şahin, ŞEYMA HANDE; MESUT, Burcu; Özsoy, Yıldız; TEKARSLAN ŞAHİN, ŞEYMA HANDE© 2017, University of Istanbul. All rights reserved.There have been advances in the cell culture models for research and drug studies. The cytotoxicity and permeability of drug molecules and delivery systems are evaluated by cell culture models both in the pharmaceutical industry and in academia. Cell models serve as an important platform to investigate cytotoxicity and permeability studies by reducing the use of animal models. Since 3D cell models mimic in vivo cells better, it plays a significant role in the testing of drugs. This review article emphasizes an overview of cytotoxicity and permeability studies and 3D cell culture model used in pharmaceutical technology.Publication Physiological and transcriptomic analysis of a salt-resistant Saccharomyces cerevisiae mutant obtained by evolutionary engineering(2018-01-01T00:00:00Z) Tekarslan-Sahin, ŞEYMA HANDE; Alkim, Ceren; Sezgin, Tugba; TEKARSLAN ŞAHİN, ŞEYMA HANDESalt-resistant yeast strains are highly demanded by industry due to the exposure of yeast cells to high concentrations of salt, in various industrial bioprocesses. The aim of this study was to perform a physiological and transcriptomic analysis of a salt-resistant Saccharomyces cerevisiae (S. cerevisiae) mutant generated by evolutionary engineering. NaCl-resistant S. cerevisiae strains were obtained by ethyl methanesulfonate (EMS) mutagenesis followed by successive batch cultivations in the presence of gradually increasing NaCl concentrations, up to 8.5% w/v of NaCl (1.45 M). The most probable number (MPN) method, high-performance liquid chromatography (HPLC), and glucose oxidase/peroxidase method were used for physiological analysis, while Agilent yeast DNA microarray systems were used for transcriptome analysis. NaCl-resistant mutant strain T8 was highly cross-resistant to LiCl and highly sensitive to AlCl3. In the absence of NaCl stress, T8 strain had significantly higher trehalose and glycogen levels compared to the reference strain. Global transcriptome analysis by means of DNA microarrays showed that the genes related to stress response, carbohydrate transport, glycogen and trehalose biosynthesis, as well as biofilm formation, were upregulated. According to gene set enrichment analysis, 548 genes were upregulated and 22 downregulated in T8 strain, compared to the reference strain. Among the 548 upregulated genes, the highest upregulation was observed for the FLO11 (MUC1) gene (92-fold that of the reference strain). Overall, evolutionary engineering by chemical mutagenesis and increasing NaCl concentrations is a promising approach in developing industrial strains for biotechnological applications.Publication Preparation and Characterization of Doripenem-Loaded Microparticles for Pulmonary Delivery(2018-12-01T00:00:00Z) Tekarslan, ŞEYMA HANDE; SAĞIRLI, Ahmet Olcay; Yildiz-Pekoz, Ayca; Akbal, Ozlem; CEVHER, Erdal; DURMUŞOĞLU, LÜTFİYE; Morina, Deniz; TEKARSLAN ŞAHİN, ŞEYMA HANDEBackground: Pneumonia is a bacterial lower respiratory tract infection that has a high morbidity rate. The gram-negative pathogen Pseudomonas aeruginosa is a significant cause of nosocomial infections and ventilator-associated pneumonias and is mainly treated by carbapenems. Doripenem is a carbapenem drug, which has a broad-spectrum antibacterial activity. The aim of this study was to develop doripenem-loaded chitosan microparticles for pulmonary administration to provide more efficient treatment for pneumonia. Methods: Ionotropic gelation and the spray-drying method were used to obtain doripenem-loaded chitosan microparticles with different lactose, trehalose, and L-leucine concentrations. Physicochemical characteristics, in vitro drug release properties, and aerodynamics properties were investigated and in vitro antimicrobial susceptibility tests of the formulations were performed. Assessment of aerodynamic properties of the powders, including Mass Median Aerodynamic Diameter, size distribution, and fine particle fraction (FPF), were performed using a Next Generation Impactor. Cytotoxicity of the fabricated microparticles was assessed using the Calu-3 cell airway epithelial cell line. Results: Optimum microparticles were produced using a combination of ionotropic gelation and spray-drying methods. Spray-dried microparticle production yield was relatively high (74.03%3.88% to 98.23%+/- 1.70%). Lactose, trehalose, and L-leucine were added to the formulation to prevent aggregation produced by the ionotropic gelation spray-drying method. Each formulation-s encapsulation efficiency was above 78.98%+/- 2.37%. The doripenem-loaded microparticle mean diameter ranged from 3.8 +/- 0.110 to 6.9 +/- 0.090m. Microparticles with 20% (w/w) L-leucine had the highest FPF ratio indicating the best aerosolization properties of the formulations. The efficacy of the formulations as an antibacterial agent was increased by forming doripenem-loaded microparticles compared to blank microparticles. P. aeruginosa showed the same susceptibility to all doripenem-loaded microparticle formulations. Cell viability of microparticles was between 70%+/- 0.08% and 90%+/- 0.04% at 0.5 and 10mg/mL concentration, respectively. Conclusions: Doripenem-loaded microparticles, produced using a combination of ionotropic gelation and spray-drying methods, are suitable for pulmonary drug delivery based on their particles size, zeta potential, cytotoxicity and high production yield. To our knowledge, this is the first study that microparticles containing doripenem were produced and characterized.Publication Targeted drug delivery and vaccinology approaches using virus-like particles for cancer(2017-01-01T00:00:00Z) Sereflioglu, Seyma; ERGİNER, Yıldız; ŞAHİN, ŞEYMA HANDE; TEKARSLAN ŞAHİN, ŞEYMA HANDENanotechnology has the potential to make significant alterations in the treatment of diseases such as cancer through targeted drug delivery nanoparticles. Virus-like particles (VLPs) are composed of the capsid proteins that do not carry the viral genome and are also noninfectious. VLPs are self-assembling competent protein structures with identical or highly related structures to their corresponding native viruses. VLPs that have precise 3D nanostructures exhibit a notable diversity in shapes and structures. They can be produced in large quantities through biological amplification and growth. External protein inserts can be displayed through genetic methods or chemical modifications. Functionalized VLPs when used as delivery systems have the ability to target with specificity and can attract macrophages for the destruction of cancer cells. The capability to target tumors for the delivery of therapeutic agents is an important goal of the design approaches of VLPs. Against the current problems in cancer therapies, delivery systems using VLPs are an arising and promising field with the potential to exhibit solutions. Cancer therapies require specific targeting of the diagnostic element or the drug to tumor cells without binding to or affecting healthy cells and tissues. Specialization of the VLPs provides an opportunity for using them as site-specific drug delivery systems in cancer therapy while reducing the systemic toxicity and the overall damage to healthy cells. With fewer side effects, immunotherapy is also a promising alternative for cancer treatment by primarily activating the host-s immune system. Cancer vaccines are aimed at inducing an immune response in the host, thereby generating a defensive mechanism against tumor cells. VLPs can be used as a vaccine without the requirement of any adjuvant due to their naturally optimized particle size and their repetitive structural order. Therefore, the aim of this review is to provide basic information about VLPs and describe previous research on VLPs used as drug and vaccine delivery systems and their applications in different types of cancer.Publication Adaptive Laboratory Evolution of Yeasts for Aroma Compound Production(2022-08-01T00:00:00Z) TEKARSLAN ŞAHİN, ŞEYMA HANDE; TEKARSLAN ŞAHİN, ŞEYMA HANDEAroma compounds are important in the food and beverage industry, as they contribute to the quality of fermented products. Yeasts produce several aroma compounds during fermentation. In recent decades, production of many aroma compounds by yeasts obtained through adaptive laboratory evolution has become prevalent, due to consumer demand for yeast strains in the industry. This review presents general aspects of yeast, aroma production and adaptive laboratory evolution and focuses on the recent advances of yeast strains obtained by adaptive laboratory evolution to enhance the production of aroma compounds.Publication Physiological and genetic analysis of cellular sodium and lithium response/resistance behavior using the yeast Saccharomyces cerevisiae as a model organism(2015-01-01T00:00:00Z) Tekarslan, ŞEYMA HANDE; Alkim, Ceren; Hunte, Carola; Çakar, Zeynep Petek; TEKARSLAN ŞAHİN, ŞEYMA HANDEThe yeast Saccharomyces cerevisiae is a simple eukaryote and an excellent model organism for molecular biology. In this study, a NaCl-resistant S. cerevisiae mutant obtained by inverse metabolic engineering was used as a model to investigate responses and resistance behavior to NaCl, LiCl, KCl, TMA, spermine and sorbitol stresses., at physiological and genetic levels. The physiological spot test results revealed that the NaCl-resistant yeast mutant showed higher resistance to LiCl and NaCl. Gene expression analysis by qRT-PCR revealed that ENA6 and NHA1 genes of the mutant were induced in the absence and presence of LiCl and NaCl. The dysfunction of Na+/H+ antiporters are related to several diseases such as hypertension, epilepsy, postischemic myocardial arrhythmia, gastric and kidney disease, diarrhea, and glaucoma. Thus, the NaCl-resistant yeast mutant could be used to understand cellular sodium and lithium resistance mechanisms and the function of Na+/H+ antiporters also in higher eukaryotic organisms, including humans.Publication Design of an amphiphilic hyperbranched core/shell-type polymeric nanocarrier platform for drug delivery(2020-01-01T00:00:00Z) ALARÇİN, EMİNE; Ozturk, Ayca Bal; Oguz, Nesrin; EMİK, Serkan; Sahin, Hande Tekarslan; TEKARSLAN ŞAHİN, ŞEYMA HANDEAn amphiphilic core/shell-type polymer-based drug carrier system (HPAE- PCL-b-MPEG), composed of hyperbranched poly(aminoester)-based polymer (HPAE) as the core building block and poly(ethylene glycol)-b-poly(epsilon-caprolactone) diblock polymers (MPEG-b-PCL) as the shell building block, was designed. The synthesized polymers were characterized with FTIR, H-1 NMR, C-13 NMR, and GPC analysis. Monodisperse HPAE-PCL-b-MPEG nanoparticles with dimensions of <200 nm and polydispersity index of <0.5 were prepared by nanoprecipitation method and characterized with SEM, particle size, and zeta potential analysis. 5-Fluorouracil was encapsulated within HPAE-PCL-b-MPEG nanoparticles. In vitro drug release profiles and cytotoxicity of blank and 5-fluorouracil-loaded nanoparticles were examined against the human colon cancer HCT116 cell line. All results suggest that HPAE-PCL-b-MPEG nanoparticles offer an alternative and effective drug nanocarrier system for drug delivery applications.Publication DORIPENEM LOADED MICROPARTICLES DELIVERY VIA PULMONARY ROUTE FOR PNEUMONIA TREATMENT(2015-08-01T00:00:00Z) Yildiz-Pekoz, Ayca; Akbal, Ozlem; Tekarslan, ŞEYMA HANDE; CEVHER, Erdal; TEKARSLAN ŞAHİN, ŞEYMA HANDE