Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Development of Keratin Based Hydrogel Systems(Izmir Institute of Technology, 2022) Yalçın Göl, Damla; Top, AybenIn this study, keratin proteins from Merino sheep wool were obtained via oxidative extraction (Chapter 2), sulfitolysis extraction (Chapter 3) and sulfitolysis with reductive extraction methods (Chapter 4). Keratin proteins were characterized XRD and FTIR spectroscopy and thermal analysis. In the SDS-PAGE gel results of the keratins diffusive protein bands between ~23 kDa and >170 kDa and a discrete band at about 12 kDa were observed confirming highly polydisperse nature of the protein samples. Then, keratin-based hydrogel systems were obtained via different methodologies. In Chapter 2, oxidized keratins (keratoses) were crosslinked with THPC to form keratose hydrogels. Effect of the amount of the crosslinking agent on the viscoelastic, swelling, and morphological properties of hydrogels was investigated. In Chapter 3, the keratin hydrogels were obtained via reformation of disulfide bridge and self-assembly of the keratin chains. In Chapter 4, keratins reduced with DTT were crosslinked with 2000 Da PEG-(C2H4-mal)2 and 6000 Da PEG-(C2H4-mal)2 to prepare PEG-hydrogels. Storage moduli of the hydrogels were obtained in the range of 63 ± 22 and 2613 ± 254 Pa and were shown to be tuned by the amount and chain length of the crosslinker. The highest swelling ratios were obtained for the THPC crosslinked hydrogels whereas the highest pore size was observed in PEG-keratin hydrogels. Cytocompatibility of the keratin based hydrogel systems was confirmed using L929 mouse fibroblast cells by applying CCK-8 tests. Of these hydrogels, PEG-keratin hydrogels were found to support cell proliferation with a higher rate than empty TCPS wells up to 4 days. These results demonstrate that low-cost keratin-based hydrogels can be used in a variety of biomedical applications, such as drug delivery systems for cancer therapy, and scaffolds in wound healing and soft tissue engineering.Master Thesis Development of Peg and Peg-Peptide Based Drug Delivery Systems(Izmir Institute of Technology, 2016) Balcı, Beste; Top, AybenIn this study, two types of drug delivery systems (DDS) were prepared; mPEG (methoxy polyethylene glycol)-HYD (hydrazide)-DOX and mPEG-peptide-(HYD)-DOX. In the design of the conjugates, mPEG was used to increase the blood circulation time. HYD provided an acid cleavable bond between the carrier molecule and DOX, whereas peptide containing histidines imparted pH responsiveness of the molecule. Doxorubicin (DOX) was selected as a model anti-cancer drug. DDS were synthesized using two steps; hydrazide functionalization of carboxylic acid of the carrier molecule followed by DOX conjugation. Hydrazide form of the carrier molecules denoted as HYD1 and HYD2 were obtained using adipic acid dihydrazide (AADH) and carbohydrazide (CH), respectively. To increase DOX conjugation, trifluoroacetic acid (TFA) and DOX amounts were changed and the reactions were carried out at the conditions giving the highest DOX conjugation (mPEG-HYD:DOX:TFA= 2.5mg:2mg:20μL per 1 mL of DMSO). The peptide (AT1=CGGGHHHHHHGGGE) was synthesized using solid phase peptide synthesis (SPPS) and PEGylated using mPEG-maleimide to obtain mPEG-AT1 conjugate. The purity of AT1 and mPEG-AT1 were confirmed using mass spectroscopy and high performance liquid chromatography (HPLC). DOX conjugation percentages were obtained as 62 7, 60 3 and 35 + 3 for mPEG-HYD1-DOX, mPEG-HYD2-DOX and mPEG-AT1-HYD1-DOX, respectively. Drug release studies indicated modest pH responsiveness of the carrier molecules obtained using AADH. On the other hand, mPEG-HYD2-DOX released 13% of drug at the end of the 72h independent of pH. For mPEG-AT1-DOX, drug release percentage values were obtained as 15% and 30% at pH 7.4 and 5.0 respectively. Cytotoxicity of the conjugates of DDS was determined using lung cancer (A-549) cell lines. DOX equivalent IC50 values were determined as 20, 40 and 5 for mPEG-HYD1-DOX, mPEG-HYD2-DOX and mPEG-AT1-DOX respectively.