Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Use of Fibroin/Hyaluronic Acid Matrices as a Drug Reservoir in Iontophoretic Transdermal Delivery(Izmir Institute of Technology, 2004) Kuduğ, Emre; Batıgün, AyşegülTransdermal drug delivery is gaining importance due to the extensive research in genetics and resulting increase of protein and peptide based drugs in the market. In order to develop materials to be used in iontophoretic transdermal drug delivery systems, various forms of silk fibroin (SF) and blending agents as hyaluronic acid (HA) have been tested for their feasibility as a potential drug reservoir. For this purpose different forms of silk such as raw silk, degummed silk fibroin, insolubilized freezedried fibroin, membranes of fibroin in pure and blended with HA were investigated for their adsorption capacities of timolol maleate, which is used as the model drug. It was found that silk fibroin and derivatives have considerable adsorption capacities for timolol maleate with 0.35 mmol per gram, comparable with commercial membranes. The insolubilization of the membranes was required for drug loading and delivery in aqueous media. Membrane insolubility was achieved by post treatment, manipulation of drying conditions, and blending with different agents. Configurational changes of fibroin protein and interactions between silk fibroin and hyaluronic acid were investigated by Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction analyses. Insoluble fibroin glutaraldehyde membranes were produced. The obtained insoluble membranes were investigated for drug delivery performance in a custom-made diffusion cell under passive diffusion and iontophoretic conditions. It was demonstrated that the silk fibroin glutaraldehyde films could be successfully used for controlled drug delivery. It was found that current densities of 1.5 and 3 mA/cm2 were suitable to accomplish controlled delivery of the drug in a pulsatile manner. The results of this study are expected to be useful in controlled transdermal delivery of positively charged drug molecules.Master Thesis Modelling and Control of Bioprocesses by Using Artificial Neural Networks and Hybridmodel(Izmir Institute of Technology, 2006) Genç, Ömer Sinan; Batıgün, Ayşegül; Batıgün, AyşegülThe aim of this study is modeling and control of bioprocesses by using neural networks and hybrid model techniques. To investigate the modeling techniques, ethanol fermentation with Saccharomyces Cerevisiae and recombinant Zymomonas mobilis and finally gluconic acid fermentation with Pseudomonas ovalis processes are chosen.Model equations of these applications are obtained from literature. Numeric solutions are done in Matlab by using ODE solver. For neural network modeling a part of the numerical data is used for training of the network.In hybrid modeling technique, model equations which are obtained from literature are first linearized then to constitute the hybrid model linearized solution results are subtracted from numerical results and obtained values are taken as nonlinear part of the process. This nonlinear part is then solved by neural networks and the results of the neural networks are summed with the linearized solution results. This summation results constitute the hybrid model of the process. Hybrid and neural network models are compared. In some of the applications hybrid model gives slightly better results than the neural network model. But in all of the applications, required training time is much more less for hybrid model techniques. Also, it is observed that hybrid model obeys the physical constraints but neural network model solutions sometimes give meaningless outputs.In control application, a method is demonstrated for optimization of a bioprocess by using hybrid model with neural network structure. To demonstrate the optimization technique, a well known fermentation process is chosen from the literature.Master Thesis Formation and Characterization of Silk Fibroin/Hyaluronic Acid Complexes and Their Use in Iontophoretic Drug Delivery(Izmir Institute of Technology, 2005) Malay, Özge; Batıgün, AyşegülThis study aimed the investigation of the pH-induced complexation of silk fibroin (SF) and hyaluronic acid (HA), and the potential use of the films casted from the aqueous mixtures of the SF-HA complexes in iontophoretic drug delivery applications.In the present study, SF-HA complex coacervation was investigated by turbidimetric, conductometric, gravimetric and viscosimetric analysis with respect to changes in total biopolymer concentration and biopolymer weight ratio. SF-HA complexes were formed within the pH-window of 2.5-3.5 regardless of the totalbiopolymer concentration, biopolymer ratio or mixing order.SF-HA aqueous complex mixtures, prepared under previously determined conditions, were casted and dried under controlled conditions. The resultant insoluble and transparent films were subjected to instrumental analysis such as DSC, XRD, FT-IR,SEM and AFM. Swelling kinetics of the films was studied for pH window of 2.5-7.4 and cyclic swelling test was performed to determine the pH-responsiveness of the films. It was shown that films swelled more in alkaline conditions and responded to the changes in pH of the medium. The permeability of the films were tested with modified-diffusion-vessels method at pH 2.5 and 7.4 and it was demonstrated that the complex films had higher permeability in alkaline condition. Eventually, iontophoretically assisted drug permeation and release studies were performed with a custom-made diffusion cell under both passive condition and electric field applied in pulsatile fashion.In conclusion, SF-HA complex films were found promising for the iontophoretic delivery of high molecular weight and charged drugs for a membrane-permeation controlled formulation. In this study, timolol maleate (TM) was used as the model drug.