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    Biyobenzer İlaçlar
    (Beykent Üniversitesi, 2020) Küçük, Çağla; Duru, Özlem Ateş; Mutlu, Esra Cansever; Sarılmışer, Hande Kazak
    Biyobenzer ilaçlar, saflık, güvenlik ve etkinlik açısından referans kaynağından klinik olarak anlamlı farklılıklara sahip olmayan lisanslı biyolojiklere (referans biyolojikler) oldukça benzer olduğu gösterilen biyolojikler olarak tanımlanmaktadır. Biyobenzerler, biyolojik kaynaklı ilaçlarla tedavisi olan hastalıklar açısından alternatif ilaçlar olarak üretilmektedir. Bu sayede kanser gibi spesifik hastalıklara yönelik tedaviler çeşitlilik kazanmaktadır. Örneğin meme kanseri için kullanılan biyobenzerler geliştirildikçe gelecekte bu hastalığın tedavilerine erişilebilirlik artacaktır ve bu gelişmeler de anti-HER2 ve anti-VEGF tedavisinin daha yaygın kullanımına olanak sağlayacaktır. Meme kanseri tedavisinde kullanılan Trastuzumab için, Avrupa patenti 2014’te, ABD patenti 2019’da sona ermiştir. Patent sürelerinin dolması bu biyobenzer ilaçların geliştirilmesini hızlandırmıştır. Bu derlemede öncelikle biyobenzerler hakkında genel bilgiler aktarılmış ve Göğüs/Meme kanseri için kullanılan biyobenzerler hakkında ayrıntılı tartışma gerçekleştirilmiştir.
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    Efficient Doxorubicin Loading to Isolated Dexosomes of Immature JAWSII Cells: Formulated and Characterized as the Bionanomaterial
    (Scilit, 2020) Mutlu, Esra Cansever; Kaya, Özge; Wood, Matthew; Mager, Imre; Topkara, Kübra; ., ve diğer.
    Immature dendritic cells (IDc), 'dexosomes', are promising natural nanomaterials for cancer diagnose and therapy. Dexosomes were isolated purely from small-scale-up production by using t25-cell-culture flasks. Total RNA was measured as 1.43 +/- 0.33 ng/10 cell. Despite the fact that they possessed a surface that is highly abundant in protein, this did not become a significant effect on the DOX loading amount. Ultrasonication was used for doxorubicin (DOX) loading into the IDc dexosomes. In accordance with the literature, three candidate DOX formulations were designed as IC50 values; dExoIII, 1.8 mu g/mL, dExoII, 1.2 mu g/mL, and dExoI, 0.6 mu g/mL, respectively. Formulations were evaluated by MTT test against highly metastatic A549 (CCL-185; ATTC) cell line. Confocal images of unloaded (naive) were obtained by CellMask(TM)membrane staining before DOX loading. Although, dexosome membranes were highly durable subsequent to ultrasonication, it was observed that dexosomes could not be stable above 70 degrees C during the SEM-image analyses. dExoIII displayed sustained release profile. It was found that dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) results were in good agreement with each other. Zeta potentials of loaded dexosomes have approximately between -15 to -20 mV; and, their sizes are 150 nm even after ultrasonication. IDcJAWSII dexosomes can be able to be utilized as the "BioNanoMaterial" after DOX loading via ultrasonication technique.
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    Exosome Production, Isolation and Characterization from A549 Epithelial Carcinoma Cells
    (Hacettepe Üniversitesi, Fen Fakültesi, 2019) Mutlu, Esra Cansever; Kaya, Özge; Yıldırım, Arzu Birinci; Çetinkaya, Ayhan
    Exosomes are natural nanoparticles that their special features as a natural, homogeneous, nanosized, targeted vesicles (~ 50- 100 nm) have started to be used in the treatment of cancer very recently They have high avidity (many conformational attachment) to attach onto targeted cancer cell surfaces. They are composed of bioactive double-layered lipid layers in which their original nature has the adhesive proteins interacting with the cancer cell membrane easily. In this study, the exosomes of non-small cell lung cancer, A549-epithelial carcinoma cells were investigated for their potential to be the natural or synthetic drug carrier. Firstly, exosomes of A549 cell line were produced using exosome-free media. Immediately after, isolation of their exosomes were performed by using ultracentrifugation procedure. Their SEM image, particle size and zeta potential measurements, exosomal RNA analysis and Protein Content by Bradford assays were performed. Findings (Size: 168 nm; zeta: -16mV) on the properties of A549 cell exosomes proved their potential to be used as the drug carrier for cancer cell therapy.
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    Improvement of antibacterial and biocompatibility properties of electrospray biopolymer films by ZnO and MCM-41
    (Springer, 2020) Mutlu, Esra Cansever; Yildirim, Arzu Birinci; Yildirm, Muhammet; Ficai, Anton; Ficai, Denisa; Oktar, Faik Nuzhet; Titu, Mihail
    This study aims the improvement of antibacterial and biocompatibility properties of electrospray ternary blends of chitosan/poly(ethylene glycol)/hyaluronic acid. It conserves microscale particle structure even after incorporating zinc oxide (ZnO), the zeolite Mobil Composition of Matter No. 41 (MCM41) and penicillin G during this technique. Three different electrospray (ESP) blend compositions (ESPI, ESPII and ESPIII) have been produced in order to improve both antibacterial activity against to bothgram-positive and gram-negativebacteria and biocompatibility. Results of FTIR spectroscopy and microscopy verified with SEM, EDS and AFM analyses. Hyaluronic acid surface has been specified definitely through ZnO-based ESPI surface composed of heterogeneously dispersed microparticles. Surface structures of ESPII and ESPIII have more homogenously dispersed microparticles as hill-valley surface by the aid of MCM 41-PEN. Antibacterial activity has been performed by Kirby-Bauer method. ESPI has good antibacterial activity against both gram-positive (S. aureusandS. epidermidis) and gram-negative bacteria (E. cloacea). Each electrospray film displayed good biocompatibility against to mouse fibroblast cell line L929 (ATTC number CCL-1). The highest amount of cell proliferation has been detected on ESPIII surface.