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    Delivery of Small Molecule EF2 Kinase Inhibitor for Breast and Pancreatic Cancer Cells Using Hyaluronic Acid Based Nanogels
    (Springer/Plenum Publishers, 2020) Cömert Önder, Ferah; Sağbaş Suner, Selin; Şahiner, Nurettin; Ay, Mehmet; Özpolat, Bülent
    Purpose To evalauted natural polymeric biomaterials including hyaluronic acid (HA) and its copolymeric form HA:Suc nanoparticles (NPs) as drug carrier systems for delivery of hydrophobic small molecule kinase EF2-kinase inhibitor in breast and pancreatic cancer cells. Methods In vitro cellular uptake studies of Rhodamine 6G labaled HA:Suc nanoparticles were evaluated by using flow cytometry analysis and fluorescent microscopy in breast (MDA-MB-231 and MDA-MB-436) and pancreatic cancer cells (PANC-1 and MiaPaca-2). Besides, in vitro release study of compound A (an EF2-kinase inhibitor) as a model hydrophobic drug was performed in the cancer cells. Results These biological evaluation studies indicated that HA and HA:Suc NPs provided a highly effective delivery of compound A were into breast and pancreatic cancer cells, leading to significant inhibition of cell proliferation and colony formation of breast and pancreatic cancer cells. Conclusion HA-sucrose NPs incorporating an EF2-Kinase inhibitor demonstrate significant biologic activity in breast and pancreatic cancer cells. This is the first study that shows natural polymeric drug carriers succesfully deliver a hydrofobic cancer drug into cancer cells. Nanoparticles based on HA:Suc are effective in delivering hydrofobic cancer drugs in breast and pancreatic cancers.
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    Hyaluronic acid and hyaluronic acid: Sucrose nanogels for hydrophobic cancer drug delivery
    (Elsevier Science Bv, 2019) Sağbaş Suner, Selin; Ari, Betül; Cömert Önder, Ferah; Özpolat, Bülent; Ay, Mehmet; Şahiner, Nurettin
    Porous and biodegradable hyaluronic acid (HA) nanogel and their copolymeric forms with sucrose (Suc), HA:Sucrose (HA:Suc) nanogels, were synthesized by employing glycerol diglycidyl ether (GDE) as crosslinker with a single step reaction in surfactant-free medium. The size of the nanogels was determined as 150 +/- 50 nm in dried state from SEM images and found to increase to about 540 +/- 47 nm in DI water measured with DLS measurements. The surface areas of HA and HA:Suc nanogels were measured as 18.07 +/- 2.4 and 32.30 +/- 6.1 m(2)/g with porosities of 3.58 +/- 1.8, and 9.44 +/- 3.1 nm via BET analysis, respectively. The zeta potentials for HA and HA:Suc nanogels were measured as -33 +/- 1.4 and -30 +/- 1.2 mV, respectively. The thermal degradation of both types of nanogels revealed similar trends, while hydrolytic degradation of the nanogels was about 22.7 +/- 02 wt% in 15 days. Both HA and HA:Suc nanogels were stable in blood up to 250 mu g/mL concentration with approximately 0.5 +/- 0.1% hemolysis ratio and 76 +/- 12% blood clotting indices, respectively. Finally, these nanogels were used as a sustained slow-release or long-term delivery system over 2 days for a hydrophobic cancer drug, 3-((E)-3-(4-hydroxyphenyl)acryloyl)-2H-chromen-2-on (A(#)) established by our group. The nanogels successfully delivered the model drug A at 10.43 +/- 2.12 mg/g for 2 days. (C) 2019 Elsevier B.V. All rights reserved.
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    Öğe
    In vitro drug release studies for the treatment of TNBC and pancreatic cancers from natural derivated polymeric micro- and nano-particles
    (Amer Chemical Soc, 2018) Cömert Önder, Ferah; Sağbaş, Selin; Ay, Mehmet; Özpolat, Bülent; Şahiner, Nurettin
    [Anstract Not Available]