Syntheses of biodegradable PLLA homopolymers and PLLA-mPEG diblock copolymers for the formation of thermo-sensitive gels were performed. The sol-gel transition temperature of the matrix was adjusted by altering the length of each PEG and LA component. PLLA-mPEG biocompatible copolymers, having appropriate length of each block component, showed sols at around 42-45 oC, suitable for the injection, then a gel with subsequent rapid cooling to body temperature. Topotecan and camptothecin were selected as anti-cancer drugs. Both drugs can easily hydrolyze at physiological conditions (pH=7.4). This causes the loss of its activity, and it turns into inactive toxic carboxylate form from active lactone state. To keep those anti cancer drugs in the lactone form, they were efficiently loaded into PLLA-mPEG gels in different loading ratios. Their stability in gel was fully examined with HPLC and fluorescence spectroscopy. It was found that both drugs were highly stable and in active form in the prepared gels (> / 95 %). Then, both release profile of drugs at different loading ratios showed prolonged release over weeks. Mechanistic studies on the stabilization of CPT anti cancer drug with PLLA-mPEG gels were carried out using ATR-FTIR, confocal and optic microscopes. The cytotoxic efficacy of TPT in the PLLA-mPEG platform (PLLA-mPEG-TPT) was evaluated on LLC-1 and 4T1 cancer cell lines by MTT assay. In vivo, the administration of PLLA-mPEG-TPT to the mice bearing breast tumours established with 4T1 cells resulted in a significant reduction in tumour size and better survival percentages. Additionally, stabilization of CPT and TPT with gels may find another application on solid tumors in brain via local injection.
A novel conducting polymer was successfully synthesized via electropolymerization of 1-(1H-pyrrol-1-yl)-2,5-di(thiophen-2-yl)-1H-pyrrole. The electrochemical and electro-optical properties of the corresponding polymer, which was the first example of polymer containing 1,1&rsquo / -bipyrrole units, were elaborated using electroanalytical and spectroscopic techniques. Cyclic voltammograms and electrooptical studies showed that the polymer has a stable and well-defined reversible redox process as well as electrochromic behavior. The processable polymer film also possessed a yellowish orange light emitter property.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/12613268/index.pdf |
| Date | 01 May 2011 |
| Creators | Mert, Olcay |
| Contributors | Demir, Ayhan S |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | Ph.D. Thesis |
| Format | text/pdf |
| Rights | To liberate the content for public access |
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