Browsing by Author "Topuzogullari, Murat"

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Core-crosslinking as a pathway to develop inherently antibacterial polymeric micelles
(WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, 2019) Kadayifci, Melike Seyma; Gokkaya, Damla; Topuzogullari, Murat; Isoglu, Sevil Dincer; Atabey, Tugba; Arasoglu, Tulin; Ozmen, Mehmet Murat; 0000-0002-6887-6549; 0000-0002-9330-5107; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
Positively charged polymeric materials have been an alternative to combat bacteria as they exhibit inherently antibacterial potency via bacteria membrane disruption. In this study, we report facile preparation of positively charged core-crosslinked polymeric micelles with inherent antibacterial properties. Spherical micelles were prepared by self-assembling of poly(4-vinylpyridine)-b-(oligoethylene glycol methyl ether methacrylate) copolymer in aqueous solution. Herein, quaternization reaction was utilized for the first time to core crosslink the micelles through the pyridine rings utilizing their hydrophobic core and thus resulting positively charged nanostructures. Dynamic light scattering (DLS) results identified that the micelles have an average hydrodynamic diameter of 114 nm with a polydispersity index ranging between 0.105 and 0.114. The electrophoretic light scattering (ELS) measurements demonstrated that the micelles have zeta potential values ranging from +38 to +63 mV. It was evident from both ELS and DLS results that the micelles in solution exhibit long-term stability as the samples were able to maintain their size and charge even after a year of storage. Further, the micelles exhibited inherently antibacterial activity against Escherichia coli and furthermore, this antibacterial efficacy was sustained over a period of 1 year. These stable core-crosslinked micelles are proposed to have great potential as antibacterial materials for long-term applications. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48393.
HER2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual pH-Sensitive DOX Release
(WILEY-V C H VERLAG GMBHPOSTFACH 101161, 69451 WEINHEIM, GERMANY, 2021) Bayram, Nazende Nur; Ulu, Gizem Tugce; Topuzogullari, Murat; Baran, Yusuf; Isoglu, Sevil Dincer; 0000-0002-8697-1654; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Bayram, Nazende Nur; Isoglu, Sevil Dincer
Here, a targeted, dual-pH responsive, and stable micelle nanocarrier is designed, which specifically selects an HER2 receptor on breast cancer cells. Intracellularly degradable and stabilized micelles are prepared by core cross-linking via reversible addition-fragmentation chain-transfer (RAFT) polymerization with an acid-sensitive cross-linker followed by the conjugation of maleimide-doxorubicin to the pyridyl disulfide-modified micelles. Multifunctional nanocarriers are obtained by coupling HER2-specific peptide. Formation of micelles, addition of peptide and doxorubicin (DOX) are confirmed structurally by spectroscopical techniques. Size and morphological characterization are performed by Zetasizer and transmission electron microscope (TEM). For the physicochemical verification of the synergistic acid-triggered degradation induced by acetal and hydrazone bond degradation, Infrared spectroscopy and particle size measurements are used. Drug release studies show that DOX release is accelerated at acidic pH. DOX-conjugated HER2-specific peptide-carrying nanocarriers significantly enhance cytotoxicity toward SKBR-3 cells. More importantly, no selectivity toward MCF-10A cells is observed compared to HER2(+) SKBR-3 cells. Formulations cause apoptosis depending on Bax and Caspase-3 and cell cycle arrest in G2 phase. This study shows a novel system for HER2-targeted therapy of breast cancer with a multifunctional nanocarrier, which has higher stability, dual pH-sensitivity, selectivity, and it can be an efficient way of targeted anticancer drug delivery.
Microwave-assisted green approach for graft copolymerization of l-lactic acid onto starch
(WILEY111 RIVER ST, HOBOKEN 07030-5774, NJ, 2016) Salimi, Kouroush; Topuzogullari, Murat; Dincer, Sevil; Aydin, Halil Murat; AGÜ, Mühendislik Fakültesi, Malzeme Bilimi ve Nanoteknoloji Mühendisliği Bölümü; Dincer, Sevil
Poly l-lactic acid grafted starch (St-g-PLA) copolymers were directly synthesized under microwave irradiation by using sodium hydroxide (NaOH) and stannous 2-ethyl hexanoate acting as a catalyst, without the use of toxic solvents. The product were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (C-13 CP/MAS NMR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA-DTG). SEM analysis indicated that microwave heating had a considerable effect on the interfacial adhesion between PLA and starch. Thermogravimetric analysis (TGA-DTG) revealed that copolymers exhibited better thermal stability. Maximum PLA grafting was achieved with the following reaction conditions: 450W microwave power, monomer ratio of 1:5 and 0.4M of NaOH. This study demonstrates that it is possible to obtain St-g-PLA copolymers with better processing characteristics and smaller sizes via microwave-assisted synthesis. The applied procedure is an interesting green synthesis method for the production of biodegradable materials used in a diverse range of applications. (c) 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42937.
A new approach for development of vaccine against visceral leishmaniasis: Lipophosphoglycan and polyacrylic acid conjugates
(ELSEVIER SCI LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND, 2017) Allahverdiyev, Adil M.; Koc, Rabia Cakir; Bagirova, Melahat; Elcicek, Serhat; Yesilkir Baydar, Serap; Oztel, Olga Nehir; Abamor, Emrah Sefik; Ates, Sezen Canim; Topuzogullari, Murat; Dincer, Sevil Isoglu; Akdeste, Zeynep; AGÜ, Mühendislik Fakültesi, Malzeme Bilimi ve Nanoteknoloji Mühendisliği Bölümü;
Objective: To determine the antileishmanial vaccine effectiveness of lipophosphoglycan (LPG) and polyacrylic acids (PAA) conjugates on in vivo mice models. Methods: LPG molecule was isolated and purified from large-scale Leishmania donovani parasite culture. Protection efficacies of LPG alone, in combination with Freund's adjuvant, in a physical mixture and in conjugate (consisting of various LPG concentrations) with PAA, were comparatively determined by various techniques, such as cultivation with the micro-culture method, assessment of in vitro infection rates of peritoneal macrophages, determination of parasite load in liver with Leishman-Donovan Units, and detection of cytokine responses. Results: Obtained results demonstrated that the highest vaccine-mediated immune protection was provided by LPG-PAA conjugate due to all parameters investigated. According to the Leishman-Donovan Units results, the sharpest decline in parasite load was seen with a ratio of 81.17% when 35 mg LPG containing conjugate was applied. This value was 44.93% for the control group immunized only with LPG. Moreover, decreases in parasite load were 53.37%, 55.2% and 65.8% for the groups immunized with 10 mg LPG containing LPG-PAA conjugate, a physical mixture of the LPG-PAA, and a mixture of LPG + Freund's adjuvant, respectively. Furthermore, cytokine results supported that Th1 mediated protection occurred when mice were immunized with LPG-PAA conjugate. Conclusions: It has been demonstrated in this study that conjugate of LPG and PAA has an antileishmanial vaccine effect against visceral leishmaniasis. In this respect, the present study may lead to new vaccine approaches based on high immunogenic LPG molecule and adjuvant polymers in fighting against Leishmania infection.
pH- and temperature-responsive amphiphilic diblock copolymers of 4-vinylpyridine and oligoethyleneglycol methacrylate synthesized by RAFT polymerization
(ELSEVIER SCI LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND, 2014) Topuzogullari, Murat; Bulmus, Volga; Dalgakiran, Eray; Dincer, Sevil; AGÜ, Mühendislik Fakültesi, Malzeme Bilimi ve Nanoteknoloji Mühendisliği Bölümü;
Diblock copolymers of 4-vinylpyridine (4VP) and oligoethyleneglycol methyl ether methacrylate (OEGMA) were synthesized for the first time using RAFT polymerization technique as potential drug delivery systems. Effects of the number of ethylene glycol units in OEGMA, chain length of hydrophobic P4VP block, pH, concentration and temperature on the solution behavior of the copolymers were investigated comprehensively. Copolymer chains formed micelles at pH values higher than 5 whereas unimeric polymers were observed to exist below pH 5, owing to the repulsion between positively charged P4VP blocks. The size of the micelles was dependent on the relative length of blocks, P4VP and POEGMA. Thermo-responsive properties of copolymers were investigated depending on the pH and length of P4VP block. The increase in the length of P4VP block decreased the LCST substantially at pH 7. At pH 3, LCST of copolymers shifted to higher temperatures due to the increased interaction of copolymers with water through positively charged P4VP block. (C) 2013 Elsevier Ltd. All rights reserved.
RAFT-mediated synthesis of poly(N-(2-hydroxypropyl)methacrylamide-b-4-vinylpyridine) by conventional and microwave heating
(SPRINGERONE NEW YORK PLAZA, SUITE 4600 , NEW YORK, NY 10004, UNITED STATES, 2013) Ozdemir, Zeynep; Topuzogullari, Murat; İsoglu, Ismail Alper; Dincer, Sevil; 0000-0003-4435-7776; 0000-0001-5085-5814; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; İsoglu, Ismail Alper; Dincer, Sevil
We report the synthesis of N-(2-hydroxypropyl)methacrylamide (HPMA) macroCTA and HPMA-b-4-Vinylpyridine block copolymers via reversible addition-fragmentation chain transfer (RAFT) reaction. Polymerization was carried out in dimethylformamide (DMF) at 70 C using 4-Cyano-4(thiobenzoylthio) pentanoic acid as chain transfer agent and AIBN as an initiator. Control over molecular weight and composition was achieved by altering the CTA, monomer and initiator feed ratio. The controlled living character of the polymerization was verified with pseudo-first-order kinetic plots, a linear increase of the molecular weight with conversion, and low polydispersities (PDIs B 1.2). Effect of microwave heating on the homo- and copolymer formation was investigated and the rates were significantly higher than those observed under conventional heating conditions. These polymerization reactions were in controlled fashion resulting in polymers with low PDIs, too. These polymers have a great potential to be used in developing delivery vehicles and conjugates for further drug or gene delivery applications
RAFT-synthesized POEGMA-b-P4VP block copolymers: preparation of nanosized micelles for anticancer drug release
(SPRINGERONE NEW YORK PLAZA, SUITE 4600 , NEW YORK, NY 10004, UNITED STATES, 2021) Bayram, Nazende Nur; Topuzogullari, Murat; Isoglu, Ismail Alper; Isoglu, Sevil Dincer; 0000-0002-8697-1654; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Bayram, Nazende Nur; Isoglu, Ismail Alper; Isoglu, Sevil Dincer
To achieve high stability and biocompatibility in physiological environment, oligoethyleneglycol methacrylate (OEGMA) and 4-vinylpyridine (4VP)-based amphiphilic block copolymers were prepared as micellar carriers to deliver doxorubicin into tumor cells. First, macroinitiator of OEGMA was synthesized by RAFT polymerization at [M](0)/[CTA](0)/[I](0) ratio of 100/1/0.2 in dimethylformamide (DMF) at 70 degrees C, in the presence of 4,4'-azobis(4-cyanovaleric acid) (ACVA) as initiator and 4-cyano-4-(thiobenzoylthio)pentanoic acid (CTA) as chain transfer agent, respectively. It was followed by copolymerization with 4-VP at similar conditions. The formation of RAFT-mediated polymers was approved by FTIR, H-1-NMR and GPC. For the preparation of drug-loaded micelles, a dialysis method was applied and hydrophobic doxorubicin, as a model drug, was entrapped into the micelles. Size distributions and morphologies of drug-loaded micelles were investigated by light scattering and scanning electron microscopy, respectively. Critical micelle concentration was estimated as 0.0019 mg/mL by measuring light scattering intensity in different polymer concentrations. Also, drug loading and entrapment efficiencies were calculated as 4.41% and 17.65% by measuring the DOX amount in the micelles, spectrophotometrically. At last, the drug-loaded micelles were applied to SKBR-3 breast cancer cell lines and revealed up to %40 cell inhibition at 48 and 72 h. As a result, these nanosized and biocompatible micelles can be used for the delivery of hydrophobic drugs, and they can also be modified for further targeting and imaging applications toward specific cancer cells.
Thermo-Responsive Complexes of c-Myc Antisense Oligonucleotide with Block Copolymer of Poly(OEGMA) and Quaternized Poly(4-Vinylpyridine)
(WILEY-V C H VERLAG GMBHPOSTFACH 101161, 69451 WEINHEIM, GERMANY, 2017) Topuzogullari, Murat; Elalmis, Yeliz Basaran; Isoglu, Sevil Dincer; 0000-0002-6871-2202; 0000-0003-4435-7776; 0000-0002-6887-6549; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
Solution behavior of thermo-responsive polymers and their complexes with biological macromolecules may be affected by environmental conditions, such as the concentration of macromolecular components, pH, ion concentration, etc. Therefore, a thermo-responsive polymer and its complexes should be characterized in detail to observe their responses against possible environments under physiological conditions before biological applications. To briefly indicate this important issue, thermo-responsive block copolymer of quaternized poly(4-vinylpyridine) and poly(oligoethyleneglycol methyl ether methacrylate) as a potential nonviral vector has been synthesized. Polyelectrolyte complexes of this copolymer with the antisense oligonucleotide of c-Myc oncogene are also thermo-responsive but, have lower LCST (lower critical solution temperature) values compared to individual copolymer. LCST values of complexes decrease with molar ratio of macromolecular components and presence of salt. Dilution of solutions also affects solution behavior of complexes and causes a significant decrease in size and an increase in LCST, which indicates possible effects of severe dilutions in the blood stream.