Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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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.Master Thesis Synthesis of Silica Nano Particles With Custom-Made Morphology for Controlled Drug Delivery(Izmir Institute of Technology, 2012) Siretli, Çağrı; Polat, MehmetThe purpose was to have nanosized particles with low energy perimeters which function as non-reacting transporters for targeted delivery along with high energy sites inside the pores to achieve controlled release of specialized chemicals. Surfactants were used in combination with both base and acid catalyzed methods to achive desired structural properties and the characterization studies such as SEM, TEM, FTIR, BET surface area, pore size, size and zeta potential measurements were conducted. The effect of surfactants on mesoporous silica production changed depending on the type of methods. In the case of base catalysed method in alcohol, formation of stabilized emulsions with different sizes and their effect on the size and shape of silica particles was proposed. The effect of surfactants was attributed to their effect on a) the emulsification process and b) silica-silica and silica-surfactant interactions involved. In the case of base catalysed silica production in water, however, surfactant micelles were used as templates to produce pores. The effect of surfactant type and concentration was attributed to their effect on the CMC, micelle shape and size. Rod-like (~400 nm) at high and spherical (~200 nm) particles at low concentrations were synthesized. Here the surface area of ~1000 m2/g and average pore size of ~3 nm were obtained. Carbonization of these materials were performed to obtain nanosized silica particles with low energy perimeters successfully. Acid catalysed silica production in water was similar. Rod-like (600-800 nm) and cubic (800-1000 nm) nanoparticles were produced. These particles exhibited lower surface area of ~700 m2/g and larger pore size of ~5 nm.