Chemical Engineering / Kimya Mühendisliği
Permanent URI for this collectionhttps://hdl.handle.net/11147/14
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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: 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: 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.