سيد حسين موسوي

In this thesis, three research studies have been conducted. In the first research study, a smart nanocarrier for drug delivery with reduced side effects and increased efficacy was introduced. NMOF-5 was rapidly synthesized using the microwave method. The particle size of NMOF-5 ranged from 18 to 20 nanometers, and its surface area was 2690 m2.g-1. The high surface area of NMOF-5 created numerous active sites for drug loading, with a drug loading percentage of 93.79%. A central composite design based on the response surface method was used to optimize drug loading conditions, and the effective parameters were eva‎luated: time = 22 minutes, dose of 5NMOF- = 9 mg, drug concentration = 80 mg.L -1 were recommended. Subsequently, 6-MP-NMOF-5 was coated with chitosan. Considering the behavior of CS-6-MP-NMOF-5 in drug release at different pH levels, it can be stated that the release of nanocarriers occurs more in the presence of cancer cells and less in normal cells, leading to a reduction in drug side effects. Kinetic studies indicated that drug release is initially controlled by chitosan swelling. However, after 8 hours of release, it follows non-fickian release. To eva‎luate the efficiency of CS-6-MP-NMOF-5, toxicity was studied in the presence of MCF-7 cell line. CS-NMOF-5 did not show significant toxicity at all concentrations. On the other hand, CS-6-MP-NMOF-5 was more toxic to MCF-7 than free 6-MP at all concentrations. In the second research study, a smart nanocarrier for oral drug delivery to reduce side effects and increase efficacy was presented. To increase drug loading capacity, IRMOF-1 was modified using APTES. This modification created numerous active sites for loading, resulting in a drug loading percentage of 97.93%. Thus, it can be said that AP-NIRMOF-1 demonstrates a high capacity for drug loading. A central composite design based on the response surface method was used to optimize drug loading conditions, and the effective parameters were eva‎luated: time = 25 minutes, dose of AP-NIRMOF-1 = 20 mg, concentration of 6-mercaptopurine = 180 mg.L-1 were recommended. Then, MERC-AP-NIRMOF-1 was coated with CMC. Using CMC achieved two important goals: 1) stability of AP-NIRMOF-1 in physiological conditions, and 2) pH-sensitive smart release of AP-NIRMOF-1. Considering the behavior of CMC-MERC-AP-NIRMOF-1 in drug release at different pH levels, it can be said that the release of the nanocarrier demonstrates smart release behavior in the intestinal environment compared to the stomach. Kinetic studies showed that the mechanism of drug release of 6-mercaptopurine by CMC-MERC-AP-NIRMOF-1 follows non-fickian (unusual) release. To eva‎luate the efficiency, the toxicity of CMC-MERC-AP-NIRMOF-1 was studied in the presence of MCF-7 and Hek293T cell lines. CMC-MERC-AP-NIRMOF-1 did not show significant toxicity at all concentrations. On the other hand, CMC-MERC-AP-NIRMOF-1 was more toxic to MCF-7 than free drug at all concentrations. In the third research study, a high-capacity adsorbent for urea and creatinine removal was prepared, which was more effective in removing urea toxins in both batch and continuous systems. By investigating Langmuir, Temkin, and Freundlich adsorption models, it was shown that the adsorbents follow the Langmuir isotherm model. A(0.2)-IR-MOF-1@SiO2 had the highest adsorption capacity for urea and creatinine (1325 and 625 mg.g-1, respectively) among all synthesized adsorbents. The presence of amino groups on the surface of A(0.2)-IR-MOF-1@SiO2 was a key factor in selecting it as the best adsorbent with the highest adsorption capacity. A longer time for saturation of urea and creatinine adsorption in the fixed-bed column of A(0.2)-IR-MOF-1@SiO2, with reported breakthrough times of 1035 and 500 minutes for urea and creatinine, respectively, was required. In this study, effective parameters, including initial internal concentration and flow rate, were also investigated. For urea and creatinine, the highest adsorption efficiency was observed at 100 and 50 ppm, respectively. The maximum adsorption efficiency for urea and creatinine at 1 min.mL-1 was observed. The experimental results obtained from this study were more similar to the Thomas model. The separation factor parameter for urea was 2.4 times higher than creatinine.

6- مركاپتوپورين، دارو رساني هوشمند، نانو چارچوب هاي فلز – آلي، سرطان، كيتوسان، كربوكسي متيل سلولز، كراتنين، اوره

6-mercaptopurine, smart drug delivery, metal-organic frameworks, cancer, chitosan, carboxymethyl cellulose, creatinine, urea.

Seyed Hossein Mousavi

Dr. Rouhollah Zare Dorabi