PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/11727/4810
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Item Magnetically responsive, sorafenib loaded alginate microspheres for hepatocellular carcinoma treatment(2020) Alpdemir, Sukran; Vural, Tayfun; Kara, Goknur; Bayram, Cem; Haberal, Erdem; Denkbas, Emir Baki; 0000-0003-2788-550X; 33010138; ABC-8833-2020This study aimed to develop sorafenib loaded magnetic microspheres for the treatment of hepatocellular carcinoma. To achieve this goal, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesised and encapsulated in alginate microspheres together with an antineoplastic agent, sorafenib. In the study, firstly SPIONs were synthesised and characterised by dynamic light scattering, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. Then, alginate-SPIONs microspheres were developed, and further characterised by electron spin resonance spectrometer and vibrating sample magnetometer. Besides the magnetic properties of SPIONs, alginate microspheres with SPIONs were also found to have magnetic properties. The potential use of microspheres in hyperthermia treatment was then investigated and an increase of about 4 degrees C in the environment was found out. Drug release studies and cytotoxicity tests were performed after sorafenib was encapsulated into the magnetic microspheres. According to release studies, sorafenib has been released from microspheres for 8 h. Cytotoxicity tests showed that alginate-SPION-sorafenib microspheres were highly effective against cancerous cells and promising for cancer therapy.Item Effect of argon plasma and Er:YAG laser on tensile bond strength between denture liner and acrylic resin(2020) Yildirim, Arzu Zeynep; Unver, Senem; Mese, Ayse; Bayram, Cem; Denkbas, Emir Baki; Cevik, Pinar; 33039186Statement of problem. The separation of a denture liner from the denture base can be a clinical problem. Different surface treatments to increase the bond have been evaluated, but studies comparing the effect of argon plasma and erbium-doped yttrium aluminum garnet (Er:YAG) laser on the bond between acrylic resin and a denture liner are lacking. Purpose. The purpose of this in vitro study was to evaluate the effect of argon plasma and Er:YAG laser treatments on the bond strengths of acrylic resin to 2 denture liners. Materials and methods. Heat-polymerized acrylic resin (Acron Duo) was bonded to silicone soft-liner materials (Molloplast B, n=30; Mollosil, n=30) to create control specimens (n=10), argon plasma treatment (n=10), and Er:YAG laser treatment (n=10). Silicone liners were polymerized on resin specimens. The tensile bond strength test was performed with a crosshead speed of 10 mm/min with a 10-N load until failure. Data were analyzed by using the Kruskal-Wallis test and unpaired t test (alpha=.05). Results. The laser group showed significantly higher bond strength than the argon plasma group for both Molloplast-B (P=.001) and Mollosil (P<.001). The highest tensile bond strength values were determined in the laser-treated Molloplast-B group (1.325 +/- 0.119 MPa) while the lowest bond strength values were determined in the Mollosil control group (0.384 +/- 0.018 MPa). Conclusions. Argon plasma and Er:YAG laser applications increases the tensile bond strength between soft-liner material and resin. Er:YAG laser treatment results in higher bond strength values than treatment with argon plasma for 1 minute.Item Silencing of survivin and cyclin B1 through siRNA-loaded arginine modified calcium phosphate nanoparticles for non-small-cell lung cancer therapy(2020) Kara, Goknur; Parlar, Ayhan; Cakmak, Melike Cokol; Coko, Murat; Denkbas, Emir Baki; Bakan, Feray; 32956996With the development of nanotechnology, various drug delivery systems including inorganic nanoparticles, liposomes, polymers, etc. have been developed over the past decade. Some of these nanoparticles are also forthcoming candidates for the successful delivery of small interfering RNA (siRNA) for targeted gene silencing. Upon its discovery, siRNA was perceived as a highly promising agent in the treatment of various diseases. However, it could not exhibit the expected clinical outcomes owing to the unfavorable challenges during delivery. One such challenge was identified as the lack of an effective carrier. Among the carriers, calcium phosphate (CaP) nanoparticles have attracted remarkable attention due to the superior biochemical properties and hold great promise for siRNA. It is well known that synthesis conditions influence the types of crystalline phases of CaPs as well as morphology. In this study, to address the influence of these parameters on the success of siRNA delivery, three different arginine (Arg) modified CaP nanoparticles having different chemical and morphological characteristics were synthesized as being the carriers of two specific siRNAs against survivin and cyclin B1. The functioning of CaP surfaces with Arg results in positive zeta potential on the surfaces. Functionalized nanoparticles have a higher loading capacity compared to unmodified particles, as they have a cationic surface that can be easily attached to negatively charged siRNAs. The gene silencing ability and the consequent in vitro antitumor activity of these CaP-Arg-siRNA complexes were investigated using A549 non-small-cell lung cancer cells. We found that high survivin and cyclin B1 expression is associated with worse survival in patients with lung cancer based on the Kaplan-Meier database. Considering the promoting role of survivin and cyclin B1 in cancer development and progression, CaP-Arg-siRNA mediated suppression of these genes resulted in a significant decrease in cell growth and induction of apoptosis. Our data suggest that all three CaP-Arg nanoparticles synthesized in this work can be used as safe and efficient nanocarriers for siRNA delivery, offering the opportunity to develop new therapeutic strategies for the treatment of lung cancer.Item 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; 30841975Purpose: 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.Item Preparation and characterization of novel albumin-sericin nanoparticles as siRNA delivery vehicle for laryngeal cancer treatment(2019) Yalcin, Eda; Kara, Goknur; Celik, Ekin; Pinarli, Ferda Alpaslan; Saylam, Guleser; Sucularli, Ceren; Ozturk, Serhat; Yilmaz, Esin; Bayir, Omer; Korkmaz, Mehmet Hakan; Denkbas, Emir Baki; 31066619Small interfering RNA (siRNA)-based gene silencing strategy has high potential on suppressing specific molecular targets, involved in cancer progression. However, the lack of an effective nanocarrier system that safely delivers siRNA to its target still limits the clinical applications of siRNA. This study aimed to develop albumin-sericin nanoparticles (Alb-Ser NPs) as a novel siRNA delivery system for laryngeal cancer treatment. Nanoparticle formulations composed of albumin and sericin at different ratios (1:1, 2:1, 1:2 w/w) were synthesized by desolvation method. The nanoparticles were modified with poly-L-lysine (PLL) for siRNA binding and decorated with hyaluronic acid (HA) to target laryngeal cancer cell line, Hep-2. HA/PLL/Alb-Ser NPs were individually loaded with siRNAs for casein kinase 2 (CK2), Absent, Small, or Homeotic-Like (ASH2L), and Cyclin D1 genes, which are overexpressed in Hep-2 cells. Downregulation of genes was confirmed by real-time PCR (RT-PCR). Size, morphological, and thermogravimetric characterizations revealed that Alb-Ser NPs having 2:1 (w/w) ratio are the most optimized formulation. Between 36.8 and 61.3% of siRNA entrapment efficiencies were achieved. HA/PLL-siRNA/Alb-Ser (2:1) NPs-mediated gene silencing resulted in a significant inhibition of cell growth and induction of apoptosis in cells. Our findings showed that HA/PLL/Alb-Ser (2:1) NPs were promising as a siRNA carrier.Item Chondrogenesis of human mesenchymal stem cells by microRNA loaded triple polysaccharide nanoparticle system(2019) Celik, Ekin; Bayram, Cem; Denkbas, Emir Baki; 31147048Degenerative 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.Item Designing siRNA-conjugated plant oil-based nanoparticles for gene silencing and cancer therapy(2019) Anilmis, Nur Merve; Kara, Goknur; Kilicay, Ebru; Hazer, Baki; Denkbas, Emir Baki; 31509450In this study, the anticancer activities of two siRNA carriers were compared using a human lung adenocarcinoma epithelial cell line (A549). Firstly, poly(styrene)-graft-poly(linoleic acid) (PS-g-PLina) and poly(styrene)-graft-poly(linoleic acid)-graft-poly(ethylene glycol) (PS-g-PLina-g-PEG) graft copolymers were synthesized by free-radical polymerization. PS-PLina and PS-PLina-PEG nanoparticles (NPs) were prepared by solvent evaporation method and were then characterized. The size was found as 150 +/- 10 nm for PS-PLina and 184 +/- 6 nm for PS-PLina-PEG NPs. The NPs were functionalized with poly(l-lysine) (PLL) for c-myc siRNA conjugation. siRNA entrapment efficiencies were found in the range of 4-63% for PS-PLina-PLL and 6-42% for PS-PLina-PEG-PLL NPs. The short-term stability test was realised for 1 month. siRNA release profiles were also investigated. In vitro anticancer activity of siRNA-NPs was determined by MTT, flow cytometry, and fluorescence microscopy analyses. Obtained findings showed that both NPs systems were promising as siRNA delivery tool for lung cancer therapy.