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  • Küçük Resim
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    Brain targeting of Atorvastatin loaded amphiphilic PLGA-b-PEG nanoparticles
    (Taylor & Francis Ltd, 2013) Simsek, Soner; Eroglu, Hakan; Kurum, Baris; Ulubayram, Kezban
    The objective of this study was to develop polysorbate 80 coated and Atorvastatin loaded poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles and to investigate advantages of coating on nanoparticles for brain delivery of Atorvastatin. The nanoparticles were prepared by nanoprecipitation method. The effects of polymer concentration, PEG content and polysorbate 80 coating on the particle size, drug loading efficiency and release behaviour of nanoparticles were investigated. Additionally, cellular uptake and brain targeting of formulated nanoparticles were studied. Particle sizes were in the range of 30-172 nm depending on formulation parameters. Increasing the polymer concentration significantly increased the nanoparticle size. Decreasing the PEG content from 15% to 5% (w/w) in polymer composition increased the nanoparticle size from 69 to 172 nm. Both coated and uncoated polysorbate 80 nanoparticles were effectively internalised within the endothelial cells. Moreover, both types of nanoparticles were able to penetrate the blood brain barrier and reach the maximum in brain 1 h post injection. It was concluded that these nanoparticles are promising nanosystems for treatment of neurological disorders.
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    Modified gold-based siRNA nanotherapeutics for targeted therapy of triple-negative breast cancer
    (Future Medicine Ltd, 2017) Shahbazi, Reza; Asik, Elif; Kahraman, Nermin; Turk, Mustafa; Ozpolat, Bulent; Ulubayram, Kezban
    Aim: In this study, we aimed to therapeutically target eukaryotic elongation factor 2 kinase (eEF-2K) in an in vivo triple-negative breast cancer (TNBC) tumor model. Materials & methods: We synthesized a highly monodisperse nanoformulation using polyethylenimine-modified gold nanoparticles (AuNP-PEI) as siRNA delivery vehicle and evaluated gene downregulation. Results: We found that AuNP-PEI/eEF-2K nanoformulation was highly effective for in vitro and in vivo gene downregulation and showed remarkable antitumor efficacy that was associated with eEF-2K knockdown, inhibition of Src and MAPK-ERK signaling pathways in a TNBC orthotopic tumor model. Conclusion: Our study suggests that eEF-2K plays an important role in TNBC tumorigenesis and its inhibition by AuNP-PEI/eEF-2K siRNA-based nanotherapeutics may be a potential therapeutic strategy for TNBC.
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    Polyethyleneimine brushes effectively inhibit encrustation on polyurethane ureteral stents both in dynamic bioreactor and in vivo
    (Elsevier Science Bv, 2017) Gultekinoglu, Merve; Kurum, Baris; Karahan, Siyami; Kart, Didem; Sagiroglu, Meral; Ertas, Nusret; Ulubayram, Kezban
    Polyurethane (PU) ureteral stents have been widely used as biomedical devices to aid the flow of the urine. Due to the biofilm formation and encrustation complications it has been hindered their long term clinical usage. To overcome these complications, in this study, cationic polyethyleneimine (PEI) brushes grafted on PU stents and their performances were tested both in a dynamic biofilm reactor system (in vitro) and in a rat model (in vivo). Thus, we hypothesized that PEI brushes inhibit bacterial adhesion owing to the dynamic motion of brushes in liquid environment. In addition, cationic structure of PEI disrupts the membrane and so kills the bacteria on time of contact. Cationic PEI brushes decreased the biofilm formation up to 2 orders of magnitude and approximately 50% of encrustation amount in respect to unmodified PU, in vitro. In addition, according to Atomic Absorption Spectroscopy (AAS) results, approximately 90% of encrustation was inhibited on in vivo animal models. Decrease in encrustation was clearly observed on the stents obtained from rat model, by Scanning Electron Microscopy (SEM). Also, histological evaluations showed that; PEI brush grafting decreased host tissue inflammation in close relation to decrease in biofilm formation and encrustation. As a results; dual effect of anti adhesive and contact-killing antibacterial strategy showed high efficiency on PEI brushes grafted PU stents both in vitro and in vivo. (C) 2016 Elsevier B.V. All rights reserved.