MOLEKÜLER BASKILANMIŞ KRİYOJEL DİSKLERDEN KURKUMİNİN KONTROLLÜ SALIMI

Abstract

In the drug research area, the way these drugs are administered to patients is as important as developing new molecules for the treatment of diseases. In recent years, controlled drug release systems have been developed in order to minimize the drug dose, extend the dosing period, and ensure that the patient is not affected by side effects. Biomaterials used to prepare controlled release systems are polymeric systems that can be obtained naturally or synthetically. Cryogels as one of these systems are three-dimensional, macroporous, networked and cross-linked gel matrices prepared using partially frozen monomer or polymer solutions. Cryogels are a widely used material in controlled drug release systems with their advantages such as high hydrophilicity, swelling without dissolving in water, biocompatibility, flexibility and high mechanical stability. Molecular imprinting technology is a method of creating intelligent polymeric systems with specific recognition sites for the template molecule, consisting of a natural or synthetic compound. The unique advantages of molecularly imprinted polymers such as their high physical and chemical stability, their feedback control mechanism, and their enantioselectivity thanks to their three-dimensional cavities specific to the template molecule cause to use in the drug release systems. Curcumin is isolated from the East Indian plant Curcuma longa, known as turmeric, which is a member of the ginger family. Curcumin is frequently involved in many applications such as antioxidant, anti-cancer, anti-microbial, anti-diabetic and anti-inflammatory activities.

In the presented thesis, curcumin-imprinted cryogel discs are prepared with different monomer ratios, different crosslinker ratios, and different drug amounts in order to examine the in vitro release of curcumin, a water-insoluble polyphenol. The polymerization efficiency of these discs is found to be 93%. The release behavior at different pH and temperature environments are investigated and pH 7.4 and 37C are determined as the most suitable release conditions. In order to determine the swelling properties of the discs, experiments are carried out at four different temperatures: 4 C, 25 C, 37 C and 42 C. The swelling and macropore ratios data are calculated. The swelling ratio of the cryogel discs are decreased with increasing the monomer ratio and crosslinker ratio. Structural characterization of curcumin-imprinted PHEMA-based cryogel discs are performed using FTIR, SEM, BET, DSC, XRD and Micro-CT. The presence of curcumin in the structure of cryogels are evaluated in the FTIR spectrum. In the SEM images of the cryogel discs, it is observed that the pore diameters decreased as the monomer ratio and different crosslinker ratio are increased. In the surface area measurements performed with the BET device, it was observed that as the monomer ratio in the structure increased, the surface area of the cryogel discs increased; as the amount of crosslinker contained in the cryogel discs increased, their surface area decreased. When the DSC thermograms are examined, it is showed that the thermal stability and the polymeric structure are amorphous in the XRD spectra; however, it is found that curcumin preserves its crystalline structure in the polymeric structure and that the drug is homogeneously dispersed in the polymeric structure. It has been interpreted that the cryogel discs with less monomer ratio in the cryogel discs whose snapshots were taken with micro-CT have a more porous structure. As the monomer ratio and crosslinker ratio are increased, the release rate and amount are decreased. The release rate is increased with increasing the amount of the monomer ratio and crosslinker ratio. With the increase of the drug-loaded amount on the polymeric structure, the driving force is increased. Therefore, with the increase of the concentration difference, the releasing amount of the drug is significantly increased. Curcumin-loaded cryogel discs are not evaluated as cytotoxic in cytotoxicity studies using the mouse fibroblast cell line L929. In cell viability studies with MDA MB 231 breast cancer cell line, dead cells are visualized by special staining method. It is concluded that cryogel discs loaded with curcumin is reduced the viability on this cell line by 75-80%. In the examination carried out to examine the antibacterial property, no zone formation is observed around the PHEMA and NIP discs without curcumin, while the formation of the zone around the curcumin-loaded MIP disc is indicated the antibacterial property of curcumin. In the imaging performed under the microscope with fluorescent attachment, it is observed that curcumin radiated due to its fluorescent property and this radiation is increased as the amount of curcumin in the structure increased. In the emission kinetic calculations, the value of n, which is the diffusion exponent, is generally found to be greater than 0.5. Accordingly, it is concluded that the diffusion mechanism is non-Fickian diffusion.