Chemical Engineering / Kimya Mühendisliği
Permanent URI for this collectionhttps://hdl.handle.net/11147/14
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Research Project pH cevaplayabilen PEG-peptid konjugatı bazlı antikanser ilaç taşıyıcı sistemleri geliştirilmesi(2016) Top, AybenBu projede kanser hücrelerinin çoklu ilaç direncine çözümüne yönelik hızlı ilaç salım kabiliyetine sahip ilaç taşıyıcı sistemlerinin geliştirilmesi amaçlanmıştır. Taşıyıcı sistemler PEG veya PEG-peptid moleküllerine model antikanser ilaç olarak kullanılan doksorubisinin (DOX) kimyasal bağla konjugasyonu ile hazırlanmıştır. PEG, taşıyıcı sistemlerde ilacın kanda dolaşım süresini arttırmak için kullanılmıştır. Peptid dizinine pH cevaplama özelliği olan histidinler ve/veya enzimatik bozunur RRALAL dizini eklenmiştir. Birinci grup taşıyıcı sistemlerinde kullanılan peptid (AT1) sadece pH cevaplama özelliği taşımaktadır ve DOX taşıyıcı sisteme asidik ortamda bozunur hidrazon bağıyla konjuge edilmiştir. DOX’un taşıyıcı sisteme kararlı amid bağıyla bağlandığı ikinci grup sistemlerde kullanılan peptid AT3, hem pH cevaplayan gruplar hem de lizozomal enzimlerde bozunur dizin içermektedir. Ayrıca kontrol sistemler olarak peptid içermeyen DOX konjuge edilmiş PEG bazlı taşıyıcı sistemler de sentezlenmiştir. Çalışmada kullanılan peptidler katı faz peptid sentezi yöntemiyle sentezlenmiş, Michael ekleme reaksiyonuyla mEG-maleimide konjuge edilmiştir. DOX taşıyıcı sistemde bulunan COOH gruplarına amid veya hidrazon bağıyla bağlanmıştır. UV spektroskopisi kullanılarak asidik ortamda bozunur bağ içeren mPEG-AT1-DOX taşıyıcı sisteminde DOX konjugasyonu %35, buna karşın DOX’un kararlı amid bağı ile konjuge edildiği mPEG-AT3-DOX sisteminde konjuge edilmemiş DOX’un ayrılamaması dolayısıyla DOX:COOH oranı % 187 olarak elde edilmiştir. Işık saçılma yöntemi kullanılarak pH 7.4’te mPEG-AT1-DOX’un boyutu 12 2 nm, mPEG-AT3-DOX’un boyutu ise 15 ve 30 nm’de ikili dağılım olarak ölçülmüştür. mPEG-AT1-DOX için nötral pH’ta % 14.5 2.5 elde edilen % DOX salımı pH 5’te % 30 7’ye yükselmiştir. Nötral pH’da % 10’un altında gözlenen mPEG-AT3-DOX’un ilaç salımı pH 5 ve katepsin B varlığında % 17 2 olarak elde edilmiştir. A549 hücre hattı kullanılarak yapılan sitotoksisite testi sonucu serbest DOX, mPEG-AT1-DOX ve mPEG-AT3-DOX’un mutlak IC50 değerleri sırasıyla 1.37 0.05, 5.55 0.75 ve 1.33 0.11 g eşdeğer DOX/ml olarak bulunmuştur.Article Citation - WoS: 5Citation - Scopus: 5Novel Biopolymer-Based Hydrogels Obtained Through Crosslinking of Keratose Proteins Using Tetrakis(hydroxymethyl) Phosphonium Chloride(Springer, 2022) Yalçın, Damla; Top, AybenMerino wool obtained from the Karacabey region of Turkey was solubilized using peracetic acid oxidation. The wool and extracted wool proteins (keratose) were characterized using SEM, XRD, TGA, and FTIR analyses. SDS-PAGE result of the keratose indicated diffusive bands were populated between ~ 40 and ~ 55 kDa, corresponding to low-sulfur content α-keratose proteins. Chemically crosslinked hydrogels were prepared using the keratose and tetrakis(hydroxymethyl) phosphonium chloride (THPC). Storage moduli of the hydrogels prepared at 1:1, 1:2, and 1:4 keratose to THPC reactive group ratios were measured as 63 ± 22, 291 ± 21, and 804 ± 53 Pa, respectively. Crosslinking degrees of the hydrogels also affected the secondary structures of the keratose films obtained from the drying of the hydrogels. The hydrogel with the highest crosslinking density (1:4 gel) exhibited the lowest swelling ratio, whereas the one with the lowest crosslinking density (1:1 gel) disintegrated in deionized water within less than 6 h. CCK-8 tests using L929 mouse fibroblast cells showed that all the hydrogels promoted cell proliferation. These results suggest THPC crosslinked hydrogels prepared at the millimolar THPC concentrations are biocompatible scaffolds, which can be utilized in drug delivery and tissue engineering applications. Graphical abstract: [Figure not available: see fulltext.]Article Citation - WoS: 3Citation - Scopus: 4Photocatalytic and Optical Properties of Zinc Oxide Structures Prepared at Different Urea Concentrations(Serban Solacolu Foundation, 2020) Uysal, Berk; Şen, Selin; Top, AybenIn this study, ZnO samples were synthesized using zinc acetate and urea with a method containing sonication, sol-gel transition and calcination steps. Urea to zinc acetate mole ratio values were changed as 0, 0.5, 1, and 2 and corresponding calcined samples were denoted as UZ-0, UZ-0.5, UZ-1, and UZ-2, respectively. Scanning electron microscopy (SEM) images indicated globular and rod-like structures. Aspect ratios of the nanorods increased as urea to zinc acetate ratio increased from 0 to 1 whereas nanoparticles with sizes of 70 +/- 20 nm were observed for UZ-2 sample. Brunauer, Emmett and Teller (BET) surface area values of the samples varied between 9 and 25 m(2)/g and increased as initial urea amount increased. Band gap energies of the samples ranged between 3.24 and 3.29 eV. Four major peaks at about 400, 420, 480 and 530 nm with different intensities were observed in the photoluminescence (PL) spectra of the samples. All the samples removed rhodamine B by both adsorption and photodegradation. The highest visible light induced photodegradation rate was exhibited by UZ-2 sample having the highest surface area and it is attributed to superior charge separation properties of this sample under visible light.Article Citation - WoS: 1Citation - Scopus: 1Potansiyel Doksorubisin Taşıyıcı Sistemi Olarak Peg-endozom Parçalayıcı Peptit Konjugatının Değerlendirilmesi(Gazi Üniversitesi, 2020) Şen, Selin; Top, AybenIn this study, it was aimed to develop a doxorubicin (DOX) carrier system based on a PEGylated TAT-derived cell penetrating peptide (G(2)RQR(3)QR(3)G(2)S) and to investigate drug release, self-assembly and stability properties of the carrier system. In the preparation of the drug delivery system, denoted as mPEG-peptide-oxime-DOX, methoxypolyethylene glycol (mPEG) with M-n=1900 Da was used. DOX was attached to the mPEG-peptide carrier system via acid cleavable oxime bond. Control drug delivery system, lack of the peptide (mPEG-oxime-DOX) was also synthesized to assess the effect of the peptide on the physicochemical and DOX release properties of the carrier system. mPEG-oxime-DOX exhibited a pH programmed DOX release with respective % DOX release values of similar to 68% and similar to 28% at pH 5.0 and at pH 7.4 at the end of 54 h. For the mPEG-peptide-oxime-DOX, on the other hand, quite low DOX release (similar to 10-15 %) was observed for both pH values suggesting possible interactions between DOX and the peptide. Initial median size value (D50) of the mPEG-oxime-DOX was measured as similar to 24 nm, independent of pH. However, for the mPEG-peptide-oxime-DOX, quite lower D50 values (similar to 3 nm and similar to 6 nm at pH 5.0 and pH 7.4, respectively) were obtained due to the repulsions between the arginines in the peptide sequence. Sizes of both drug delivery systems, tended to increase upon incubation at physiological conditions for 1 day suggesting that longer PEG chains should be used to enhance the stability of the mPEG-peptide-oxime-DOX and mPEG-oximeDOX systems.Article Citation - WoS: 4Citation - Scopus: 4Optical and Photocatalytic Properties of Zno and Zns Structures Formed as Controlled Calcination Products of L-Cysteine Assisted Aqueous Precipitation(Elsevier, 2020) Şen, Selin; Top, AybenZnO and ZnS structures were obtained by the calcination of the aqueous precipitation products of Zn(NO3)2, NaOH and L-cysteine (Cys). Initial Cys:Zn molar ratios were changed as 0.1:1, 0.5:1, 1:1 and 1.5:1. All the precursors were transformed into ZnO upon calcination at 700 °C. ZnS structures were obtained by calcining the precursors prepared at the Cys:Zn ratios of 1 and 1.5 at 350 °C. In addition to changing chemical composition of the precipitation products, calcination temperature and initial Cys:Zn ratio also affected morphology, surface area, photoluminescence and photocatalytic properties of the final products. Free exciton energy values of the ZnO samples were observed to be between 3.29 eV and 3.35 eV. PL spectra of the ZnO samples indicated blue and green emission centers. Zinc interstitials (Zni), revealed by the blue emissions in the PL spectra were also confirmed by Auger Zn L3M4.5M4.5 spectra. The samples calcined at 350 °C removed rhodamine B mainly by adsorption. All the samples calcined at 700 °C successfully degraded the dye under UV light. Among the samples calcined at 700 °C, ZnO sample prepared at Cys:Zn = 0.5, which has the highest surface area and unique photoluminescence spectrum exhibited the fastest photodegradation rate. © 2020 Elsevier LtdArticle Citation - WoS: 24Citation - Scopus: 26Self-Assembly Behavior of the Keratose Proteins Extracted From Oxidized Ovis Aries Wool Fibers(Elsevier Ltd., 2019) Pakkaner, Efecan; Yalçın, Damla; Uysal, Berk; Top, AybenWater soluble keratose proteins were obtained from an Ovis Aries wool using peracetic acid oxidation. The wool samples and the extracted keratose proteins were characterized by using FTIR, XRD, SEM and TGA techniques. Fractions of alpha-keratose (MW = 43-53 kDa) along with protein species with molecular weights between 23 kDa and 33 kDa were identified in the SDS-PAGE analysis result of the extracted protein mixture. DLS and AFM experiments indicated that self-assembled globular nanoparticles with diameters between 15 nm and 100 nm formed at 5 mg/ml keratose concentration. On the other hand, upon incubation of 10 w % keratose solutions at 37 degrees C and 50 degrees C, interconnected keratose hydrogels with respective storage modulus (G') values of 0.17 +/- 0.03 kPa and 3.7 +/- 0.5 kPa were obtained. It was shown that the keratose hydrogel prepared at 37 degrees C supported L929 mouse fibroblast cell proliferation which suggested that these keratose hydrogels could be promising candidates in soft tissue engineering applications. (C) 2018 Elsevier B.V. All rights reserved.Article Citation - WoS: 12Citation - Scopus: 12Peg and Peg-Peptide Based Doxorubicin Delivery Systems Containing Hydrazone Bond(Springer Verlag, 2018) Balcı, Beste; Top, AybenmPEG and mPEG-peptide based drug delivery systems were prepared by conjugating doxorubicin (DOX) to these carrier molecules via hydrazone bond. The peptide, AT1, with a sequence of CG3H6G3E served as mPEG and doxorubicin attachment site. Histidines were incorporated to the sequence to improve pH responsiveness of the carrier molecule. Hydrodynamic diameters (mean sizes) of mPEG-based drug delivery system (mPEG-HYD-DOX) were measured as 9 ± 0.5 and 7 ± 0.5 nm at pH 7.4 and pH 5.0, respectively. Mean size of the aggregates of the peptide containing drug delivery system, mPEG-AT1-DOX, was determined as 12 ± 2 nm at neutral pH. At pH 5.0, on the other hand, mPEG-AT1-DOX exhibited a size distribution between 20 and 100 nm centered at about 40 nm. Comparison of % DOX release values of the drug delivery systems obtained at pH 7.4 and pH 5.0 indicated that mPEG-AT1-DOX has enhanced pH sensitivity. DOX equivalent absolute IC50 values were obtained as 0.96 ± 0.51, 21.9 ± 5.9, and 5.55 ± 0.75 μg/mL for free DOX, mPEG-HYD-DOX, and mPEG-AT1-DOX, respectively. Considering more pronounced pH sensitivity and cytotoxicity of mPEG-AT1-DOX, the use of both pH responsive functional groups and acid cleavable chemical bond between the carrier molecule and drug can be a promising approach in the design of drug delivery systems for cancer therapy.Article Citation - WoS: 4Citation - Scopus: 4PEG-peptide conjugate containing cathepsin B degradation unit as a doxorubicin carrier system(TUBITAK, 2018) Şentürk, Nesligül; Top, AybenA drug delivery system (DDS) containing a cathepsin B degradable sequence and pH-responsive histidines was prepared by methoxypolyethylene glycol and peptide conjugation. Doxorubicin was attached to the carrier system using amide linkage to give the final form of the DDS, denoted as mPEG-AT3-DOX. mPEG-AT3-DOX exhibited a bimodal size distribution at about 15 and 30 nm independent of pH, whereas the size of the control DDS containing no peptide sequence, mPEG-DOX, was measured as ∼ 15–20 nm. At the end of 72 h, % doxorubicin release from both of the DDSs was observed to be below 8.5 ± 3% in the absence of cathepsin B, and it increased to 17 ± 2% in the presence of cathepsin B for mPEG-AT3-DOX. Complete degradation of AT3 peptide within 3 h upon incubation with cathepsin B suggests that lower than expected doxorubicin release is likely due to the aggregation tendency of mPEG-AT3-DOX. Absolute IC50 values indicated that the cytotoxicity trend of the samples is in the order of free DOX ≥ mPEG-AT3-DOX >mPEG-DOX. Considering these results, PEG-peptide-doxorubicin conjugates can be promising candidates in cancer therapy if they are designed to have more pronounced pH-responsive behavior to increase the drug release rate.Article Citation - WoS: 73Citation - Scopus: 77Zinc Oxide and Zinc Hydroxide Formation Via Aqueous Precipitation: Effect of the Preparation Route and Lysozyme Addition(Elsevier Ltd., 2015) Top, Ayben; Çetinkaya, HayrullahAqueous precipitation products of Zn(NO3)2 and NaOH obtained by changing the method of combining the reactants and by using lysozyme as an additive were investigated. In the case of single addition method, octahedral ε-Zn(OH)2 and plate-like β-Zn(OH)2 structures formed in the absence and in the presence of lysozyme, respectively. Calcination of these Zn(OH)2 samples at 700 °C yielded porous ZnO structures by conserving the template crystals. When zinc source was added dropwise into NaOH solution, predominantly clover-like ZnO crystals were obtained independent of lysozyme addition. Mixed spherical and elongated ZnO morphology was observed when NaOH was added dropwise into Zn(NO3)2 solution containing lysozyme. Lysozyme contents of the precipitation products were estimated as in the range of ∼5-20% and FTIR indicated no significant conformational change of lysozyme in the composite. These results suggest that lysozyme-ZnO/Zn(OH)2 composite materials may have a value as an antibacterial material.Article Citation - WoS: 25Citation - Scopus: 25Conformational and Aggregation Properties of a Pegylated Alanine-Rich Polypeptide(American Chemical Society, 2011) Top, Ayben; Roberts, Christopher J.; Kiick, Kristi L.The conformational and aggregation behavior of PEG conjugates of an alanine-rich polypeptide (PEG-c17H6) were investigated and compared to that of the polypeptide equipped with a deca-histidine tag (17H6). These polypeptides serve as simple and stimuli-responsive models for the aggregation behavior of helix-rich proteins, as our previous studies have shown that the helical 17H6 self-associates at acidic pH and converts to β-sheet structures at elevated temperature under acidic conditions. In the work here, we show that PEG-c17H6 also adopts a helical structure at ambient/subambient temperatures, at both neutral and acidic pH. The thermal denaturation behavior of 17H6 and PEG-c17H6 is similar at neutral pH, where the alanine-rich domain has no self-association tendency. At acidic pH and elevated temperature, however, PEGylation slows β-sheet formation of c17H6, and reduces the apparent cooperativity of thermally induced unfolding. Transmission electron microscopy of PEG-c17H6 conjugates incubated at elevated temperatures showed fibrils with widths of ∼20-30 nm, wider than those observed for fibrils of 17H6. These results suggest that PEGylation reduces β-sheet aggregation in these polypeptides by interfering, only after unfolding of the native helical structure, with interprotein conformational changes needed to form β-sheet aggregates.