Fakülteler / Faculties

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    Fabrication of Monodispersive Nanoscale Alginate-Chitosan Core-Shell Particulate Systems For Controlled Release Studies
    (2014) Korpe, Didem Aksoy; Malekghasemi, Soheil; Aydin, Ugur; Duman, Memed
    Biopolymers such as chitosan and alginate are widely used for controlled drug delivery systems. The present work aimed to develop a new protocol for preparation of monodisperse alginate-coated chitosan nanoparticles at nanoscale. Modifications of preparation protocol contain changing the pH of polymer solutions and adding extra centrifugation steps into the procedure. While chitosan nanoparticles were synthesized by ionic gelation method, they were coated with alginate by electrostatic interaction. The size, morphology, charge, and structural characterization of prepared core-shell nanoparticulated system were performed by AFM, Zeta sizer, and FTIR. BSA and DOX were loaded as test biomolecules to core and shell part of the nanoparticle, respectively. Release profiles of BSA and DOX were determined by spectrophotometry. The sizes of both chitosan and alginate-coated chitosan nanoparticles which were prepared by modified protocol were measured to be 50 +/- 10 and 60 +/- 3 nm, respectively. After loading BSA and DOX, the average size of the particles increased to 80 +/- 7 nm. Moreover, while the zeta potential of chitosan nanoparticles was positive value, the value was inverted to negative after alginate coating. Release profile measurements of BSA and DOX were determined during 57 and 2 days, respectively. Our results demonstrated that monodisperse alginate-coated nanoparticles were synthesized and loaded successfully using our modified protocol.
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    Transscleral Delivery of Bevacizumab-Loaded Chitosan Nanoparticles
    (2019) Ugurlu, Nagihan; Asik, Mehmet Dogan; Cakmak, Hasan Basri; Tuncer, Sema; Turk, Mustafa; Cagil, Nurullah; Denkbas, Emir Baki; 30841975
    Purpose: The aim of this study was to synthesize bevacizumab-loaded nanoparticles and evaluate their effects on the treatment of posterior segment diseases via subtenon injections. Methods: Bevacizumab-loaded chitosan nanoparticles (BLCNs) were synthesized by the ionic gelation method, and their physicochemical characteristics and in vitro release profile were studied. The BLCNs were characterized using atomic force microscopy (AFM), FTIR spectroscopy, dynamic light scattering, and scanning electron microscopy. The BLCNs were delivered into rabbits' eyes via posterior subtenon injections. An immunohistochemical evaluation of the ocular tissues was performed, and the vitreous humor and serum bevacizumab levels were measured by ELISA. Results: Bevacizumab-loaded chitosan nanoparticles with a diameter of 80 to 380 nm were prepared and characterized. In vitro studies showed that after the first 5 days of the experiment, a significant increase in the drug release maintained the desired drug dosage for 3 weeks. Immunohistochemical in vivo studies revealed that there were BLCNs penetrating through the sclera. Furthermore, the intravitreal bevacizumab concentration reached a maximum concentration of 18 mu g/ml, and it decreased to 6 mu g/ml after only a week. Conclusion: The results revealed that subtenon injection of BLCNs is a promising alternative to intravitreal injections. In addition to the ELISA studies, immunohistochemical experiments confirmed that BLCNs enable transscleral bevacizumab penetration, and BLCN usage may provide the required bevacizumab levels for the treatment of posterior segment diseases.
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    Chondrogenesis of human mesenchymal stem cells by microRNA loaded triple polysaccharide nanoparticle system
    (2019) Celik, Ekin; Bayram, Cem; Denkbas, Emir Baki; 31147048
    Degenerative cartilage is the pathology of severe depletion of extracellular matrix components in articular cartilage. In diseases like osteoarthritis, misregulation of microRNAs contributes the pathology and collectively leads to disruption of the homeostasis. In this study chondroitin sulfate/hyaluronic acid/chitosan nanoparticles were prepared and successfully characterized chemically and morphologically. Results demonstrated higher chondroitin sulfate amounts led smaller nanoparticles, but lower surface zeta potential due to high electronegativity. After optimization of chondroitin sulfate amounts regarding size and charge, nanoparticles were loaded with microRNA-149-5p, a therapeutic miRNA downregulated in osteoarthritis, and evaluated focusing on their loading efficiency, release behaviour, cytotoxicity and gene transfection efficiency in vitro. Results showed all nanoparticle formulations were non-toxic and promising gene delivery agents, due to increased levels of microRNA-149-5p and decreased mRNA levels of microRNA's target, FUT-1. Highest gene transfection efficiency was obtained with the nanoparticle formulation which had the highest chondroitin sulfate load and smallest size. In addition, owing to their high chondroitin sulfate cargo, all nanoparticles were reported to enhance chondrogenesis, which was demonstrated by gene expression analysis and sulfated glycosaminoglycan (sGAG) staining. The obtained data suggest that the delivery of microRNA-149-5p via polysaccharide based carriers could achieve collaborative impact in cartilage regeneration and have a potential to enhance osteoarthritis treatment.