PH Duyarlı Çoklu İlaç Salımı İçin Metal Organik Çerçeve Temelli Mikro Kapsüllerin Hazırlanması ve Karakterizasyonu

Abstract

One of the most important points in the design and preparation of drug delivery systems is the synergistic provision of multiple therapeutic effects. Providing synergistic effects, especially in cancer treatment studies, is an issue that has gained importance and focused on in recent years. In this way, it is aimed to eliminate the limitations of monotherapy, to make the treatment effective and to provide maximum effect with the least drug/chemical dose. Vesicles are structures that have been studied for many years with their lipid and aqueous compartments, their biocompatibility and ability to encapsulate and transport even macromolecules. In addition to their drug carrier properties, vesicles can be designed to provide synergistic effects with their hydrophilic and hydrophobic components. In the first part of the study, a vesicle that can perform Fenton reactions, which is an important type of chemodynamic therapy methods, was synthesized. A surfactant, N,N-dimethylferrocenylmethylundecyl ammonium bromide (Fc(C11)) has been used as the fenton agent. This surfactant has been used as one of the vesicle forming molecules and is located in the bilayer of the vesicle, allowing us to leave the aqueous core as a potential reservoir. Cationic Fc(C11) and anionic sodium dioctylsulfosuccinate (AOT) were used to obtain a catanionic vesicle Characterization of vesicles was performed using dynamic (DLS) and static light scattering (SLS).Monomeric Fc(C11) and vesicle Fc(C11)- The performance of AOT fenton reaction was investigated by methylene blue removal method. The data were analyzed by applying different kinetic models. As a result of the experiments, chemodynamic therapy agent vesicles were obtained that successfully carried out the fenton reactions. The second step of the study was the synthesis and development of zeolitic imidazolate framework-8 (ZIF-8). ZIF-8 is one of the main components of this drug delivery system. ZIF-8 is a type of MOF that has been studied in many areas from gas separation to catalysis processes since its discovery, with its advantages such as high porosity, chemical and thermal stability. However, in the last decade, it has become a prominent crystal structure in drug transport studies with its pH sensitive structure. Within the scope of the study, ZIF-8 was synthesized as a potential chemotherapy agent carrier that can make pH sensitive controlled release. The "one-pot" method was used to load rhodamine-b (Rhb) into ZIF-8 as the model molecule. ZIF-8 synthesis was carried out in solvent environments such as methanol and water, and the amount of zinc, imidazole and rhodamine-b was studied parametrically. The release of rhodamine-b was carried out in phosphate buffer solutions with different pH and the rhodamine uptake-release performance of ZIF-8 crystals was investigated. Potential chemotherapy agent particles were obtained with the ability of ZIF-8 crystals to successfully encapsulate and release (Rhb@ZIF-8) pH- sensitive rhodamine-b, which is used as a model molecule. Then, in order to increase the synergistic effect, polydopamine (PDA) with photothermal therapy effect was coated on ZIF-8 crystals. The PDA coating was provided by the polymerization of dopamine hydrochloride (DA-HCl) directly on the ZIF-8 surface in alkaline medium. Tris buffer solution was used in the coating and a ratio of 1:1 by weight of DA-HCl:ZIF-8 was used. The photothermal effect of the obtained particles (Rhb@ZIF-8/PDA) was followed by a thermal camera under a laser with a wavelength of 808 nm. It has been observed that the particles provide the necessary temperature increase for photothermal therapy even at low concentrations. ZIF-8, Rhb@ZIF-8 and Rhb@ZIF-8/PDA particles were characterized by DLS, AFM, TEM, XRD and FTIR and zeta potential measurements. In the final stage of the study, chemodynamically effective vesicles and ZIF-8 crystals with photodynamic and chemotherapeutic effects were combined by utilizing electrostatic interactions. Rhodamine-b release and Fenton reaction performance of the obtained drug delivery system were performed as mentioned above. As a result of the study, a multifunctional drug delivery system with chemodynamic, photothermal and chemotherapeutic effects was obtained with Rhb@ZIF-8/PDA coated on the outer surface of Fc(C11)-AOT vesicles.