Phd Degree / Doktora

Permanent URI for this collectionhttps://hdl.handle.net/11147/2869

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  • Doctoral Thesis
    Development of Novel Chitosan Nanocomposites as a Controlled Drug Release System for Helicobacter Pylori Treatment
    (İzmir Institute of Technology, 2016) Güneş, Suna Seda; Tıhmınlıoğlu, Funda; Yılmaz, Özlem
    Helicobacter pylori is one of the most common bacterial infection and responsible for gastroduodenal diseases in humans. Due to increasing failure rate of currently used antibiotic therapies, newer drugs and therapeutic approaches are needed. Therefore the use of encapsulated cinnamon bark oil is a promising approach for H. pylori eradication. The main objective of this dissertation was to develop a novel drug delivery system using chitosan and nanoclay containing cinnamon bark oil to be released in a controlled manner in gastrointestinal system for H. pylori eradication as an alternative or complementary to conventional antibiotic treatment. Minimum inhibition concentration (MIC) value of cinnamon bark oil was determined. Cinnamon bark oil loaded chitosan nanocomposite microspheres were produced by spray drying. The prepared microspheres were characterized for particle size & morphology, encapsulation efficiency, surface charge, mucoadhesion, degradation, swelling and drug release. Antimicrobial activity of the microspheres against H. pylori were investigated. In vitro cell viability of fibroblast and gastric epithelial cells were evaluated. In vitro cellular uptake and binding studies of microspheres were investigated by using gastric epithelial cells. MIC value of cinnamon bark oil was found as 8 μg/mL. Nanoclay incorporation decreased the biodegradation of nanocomposite microspheres and improved the release of cinnamon bark oil. Drug release mechanism was anomalous diffusion which refers to combination of diffusion and erosion controlled. The prepared microspheres showed strong mucoadhesive property. Oil released from prepared microspheres inhibited H. pylori growth. Although cinnamon oil showed cytotoxic effect above 31 μg/mL, the oil encapsulated chitosan microspheres did not show any cytotoxic effect on NIH3T3 and MKN45 cells. The prepared microspheres were able to get internalized into MKN45 cells and had great incorporation activity. The results of this study demonstrated that cinnamon bark oil loaded chitosan nanocomposites may serve as biocompatible and effective gastroretentive drug carrier for the treatment of H. pylori infection.
  • Doctoral Thesis
    Natural and Synthetic Silica Incorporated Chitosan Composite Scaffolds for Bone Tissue Engineering Applications
    (İzmir Institute of Technology, 2016) Tamburacı, Sedef; Tıhmınlıoğlu, Funda; Tıhmınlıoğlu, Funda; Havıtçıoğlu, Hasan
    Recently bone tissue engineering studies have focused on the development of 3D scaffolds that can organize the tissue regeneration in natural way with appropriate porosity and reinforced the structure. Natural polymer-based composites have been focused with more attention than synthetic polymer composites for bone tissue engineering applications because of their biocompatibility and biodegradability. In this work, the goal was to combine the useful biomaterial properties of both chitosan and silica to design biocomposite organic/inorganic biomaterials for bone tissue engineering applications. The composite scaffolds were fabricated by freeze drying method bu using two different silicas; natural silica; Diatomite and synthetic silica, octa (tetramethylammonium) polyhedral oligomeric silsesquioxanes (OctaTMA-POSS). The effects of silica type and loading on the mechanical, morphological, chemical, surface properties, wettability and biocompatibility of composite scaffolds were investigated and characterized by using SEM, AFM, contact angle analysis, swelling study, protein adsorption assay, biodegradation and biomineralization tests. WST-1 cytotoxicity, cell proliferation with rezasurin and alkaline phosphatase activity assays were performed to determine biological activity of the composite scaffolds. In vitro biomineralization on scaffolds was determined by Von Kossa and Alizarin red staining. POSS and diatomite incorporation increased the surface roughness. Chitosansilica composites exhibited 82-90% porosity. Wet chitosan-silica composite scaffolds exhibited higher compression moduli compared to pure chitosan scaffold in 67.3- 81.4kPa and 78.1 to 107.6kPa range respectively. Average pore size range of chitosandiatomite and chitosan-POSS composite scaffolds was obtained as 15-180μm and 220- 300μm, respectively. Results indicated that chitosan-silica composites did not show any cytotoxic effect on 3T3, MG-63 and Saos-2 cell lines. Chitosan-silica composites were found to be favorable for osteoblast proliferation. Diatomite and POSS incorporation showed promising effects with enhancing ALP activity on hFob cells. Therefore, these composite scaffolds could be used for bone tissue engineering applications.