KANSER TEDAVİSİNDE KULLANILAN RESVERATROLÜN İLAÇ TAŞIYICI SİSTEM OLARAK KİTOSAN-ALJİNAT KOMPOZİT BİYOJELLERE YÜKLENMESİ VE SALIMININ İNCELENMESİ

Abstract

In this thesis, Ca - Alginate spheres, Alginate - Chitosan hybrid spheres and resveratrol cross - linked chitosan nanoparticles were synthesized. By using chitosan and alginate biopolymers, biocomposite spheres were synthesized and chitosan and alginate properties were combined to obtain drug delivery systems with superior properties of both components. The anionic alginate and the cationic chitosan combine to form a polyelectrolyte complex and composite spheres are synthesized using the "drip technique". In the study, resveratrol-loaded chitosan nanoparticles were synthesized by "cross-linking technique". The synthesized Ca - Alginate spheres and Alginate - Chitosan hybrid spheres were investigated release profiles and loaded with resveratrol drug which is using in the therapy of cancer. In addition, resveratrol release from synthesized resveratrol cross-linked chitosan nanoparticles was investigated. The encapsulation efficiencies, loading capacities and cumulative release of the particles were determined. The highest encapsulation was obtained in hybrid spheres with a mass ratio of 1: 1 and was found to be 96%. Resveratrol is a polyphenolic compound from the family of stilbene, which is of great importance in the treatment of cancer. Encapsulation is intended to increase the dispersibility of water in resveratrol, increase chemical stability, increase bioavailability when taken orally, increase pH stability, and increase UV stability. Free resveratrol concentration measurements were made using a UV detector Thermo Scientific Dionex Ultimate 3000 HPLC, and the absorbance required for the assay was found to be 306 nm. In order to establish the in vivo medium for resveratrol release values from the particles phosphate buffer and hydrochloric acid buffers were used. Resveratrol release was studied in 1.2 - 5.5 - 6.8 - 7.4 buffer solutions with pH levels of the gastrointestinal tract. Characterization studies of the synthesized particles were carried out using Fourier Transform Infrared Spectroscopy (FTIR) and the physical and chemical changes during the heating of the particles were investigated in thermogravimetric analyzer (TGA) and differential scanning calorimetry (DSC). Surface and pore structures of Ca - Alginate spheres and Alginate - Chitosan hybrid spheres were determined by BET analysis. Scanning electron microscopy (SEM) was also used to determine the morphology of the particles. Swelling behavior of Ca - Alginate spheres and Alginate - Chitosan hybrid spheres prepared at different mass ratios were determined at different pH buffers. Composite mass ratio, drug amount and pH value effect of resveratrol release from alginate - chitosan hybrid spheres were investigated. The results of the studies were obtained in Alginate - Chitosan hybrid spheres with a mass ratio of 1: 2 with 70 mg resveratrol loaded at the highest release pH of 5.5. In the 1: 2 mass ratio Alginate - Chitosan hybrid spheres, in order to determine the drug release mechanism and to analyze mathematically; Zero-order, First-order, Higuchi, Korsmeyer - Peppas and Baker-Lonsdale drug delivery kinetics models the compatibility of the release data at different pH values has been investigated. The in-vitro data obtained were fitted to kinetic models to calculate R^2, k and n diffusing exponents. According to the obtained R^2 values, it was determined that the drug release better conformed to the Korsmeyer - Peppas release kinetic model.