İlaç Taşıyıcı Olarak Halloysit İçeren Nanosüngerlerin Tasarımı, Sentezi ve Karakterizasyonu

Abstract

Nanomaterials are of significant importance in many industries today due to their special properties and usage areas. Due to their small size and high surface area-to volume ratios, nanomaterials exhibit unique characteristics. The development of a targeted drug delivery system is a result of recent advancements in nanotechnology. However, the successful targeting of a molecule to a specific region requires a specialized drug delivery system. The development of nanosponges (NS) based on nanomaterials, capable of hosting both hydrophilic and hydrophobic drugs, has become a crucial step in addressing certain issues such as drug toxicity, low bioavailability, and drug transportation. The porous structure of nanosponges grants them a unique ability to trap drug molecules and facilitate their transportation as desired. Nanosponges are nano-sized, viscoelastic structures capable of moving towards target areas in the body and adhering to surfaces to facilitate the transportation of drugs in the desired manner. Due to their unique structures, nanosponges can absorb a wide variety of chemicals. One of the most significant features of nanosponges is their high surface area. Their structures allow them to contain numerous pores per unit volume, enabling them to absorb materials in liquid or gas states. The applications of nanosponges are diverse, including drug delivery, medical applications, environmental remediation, tissue engineering, and materials science. For instance, nanosponges can be used in biomedicine to target specific areas or accelerate wound healing. The properties and applications of nanosponges play a vital role in the novel solutions provided by nanotechnology. The primary aim of this thesis is to utilize β-cyclodextrin (βCD) based nanosponges synthesized with different binders to enhance the passive transportation and reduce the side effects of hydroxyurea, commonly used in cancer treatment. Additionally, by conjugating the synthesized nanosponge materials with halloysite clay, a nanomaterial with a significantly increased surface area and enhanced drug binding capacity is obtained. Three different nanosponge materials are synthesized in the presence of maleic anhydride (MA), epichlorohydrin (EPI), and maleic anhydride-epichlorohydrin (MA-EPI), using a solution method, and their interactions with halloysite are realized through in-situ and ex-situ methods. Three different structures of nanosponge-drug conjugates were obtained, and the interaction of these three different nanosponge structures with drugs was compared between nanosponge clay nanocomposites obtained after the addition of HNT and nanosponge structures without HNT addition. Additionally, by investigating the properties of nanosponge structures in conjunction with cross-linkers, differences between materials have been identified, and nanosponge structures with the least toxic effects have been determined. In the thesis study, nanosponges containing maleic anhydride structures were compared with nanosponges containing epichlorohydrin structures, which are highly toxic due to the lesser toxic effect of maleic anhydride structure. The structures of all synthesized materials are elucidated using Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR), Proton Nuclear Magnetic Resonance (1H-NMR), and X-Ray Photoelectron Spectroscopy (XPS). Thermal Gravimetric Analysis (TGA) is utilized to examine the decomposition temperatures of the synthesized materials. Dynamic Mechanical Analysis (DMA) provides insights into the dynamic mechanical structure of the material by providing information on the glass transition temperature and thermal transitions of nanomaterials. Scanning Electron Microscopy (SEM) analysis is conducted to examine the surface morphology of nanomaterials. In this thesis study, the cellular effects of synthesized nanosponge-hydroxyurea conjugates are evaluated on HEK293 cells, human embryonic kidney cells. Through cytotoxicity experiments, the intra-cellular interactions and effects on cells of the conjugates are investigated to determine potential biomedical applications. The findings obtained contribute to the understanding of the effectiveness of nanosponge hydroxyurea conjugates on cells and lay a foundation for future studies.