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Synthesis and Characterization of Metal-Organic Frameworks (Gadolinium Base) Carrying Quercetin Drug to Evaluate Memory Impairment in White Rats

Tajahmadi, Shima | 2023

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 56893 (48)
  4. University: Sharif University of Technology
  5. Department: Institute for Nanoscience and Nanotechnology
  6. Advisor(s): Shamloo, Amir; Shojaei, Akbar; Sharifzadeh, Mohammad
  7. Abstract:
  8. One of the diseases of the central nervous system that are included in the neurodegenerative disorders and its impressive expansion among the people of the world and Iran is an alarming to us, is Alzheimer's disease. Since the cause of the disease has not yet been precisely determined, there is no definite cure for this disease yet. However, an important indicator in the disease is its early diagnosis so that the disease can be controlled and prevented from progressing in the early stages and before the degeneration of neurons. The big challenge that is observed in the diagnosis and effectiveness of drugs in this disease and any type of central nervous system disorder is the existence of the physical barrier of the blood-brain membrane (BBB), which prevents the entry of drug molecules and imaging contrast agents into the brain tissue. In this project, nanoparticles of metal-organic framework (MOF) carrying drug (quercetin) are designed based on the combination of gadolinium (Gd) metal. The designed Gd-MOF can pass through BBB as drug carrier and imaging agant. After synthesizing amine-free and amine modified of Gd-MOFs by the solvothermal method, activation of MOFs are investigated by various solvents, different methods and over different time peroids. Among the amine-free Gd-MOFs, 3d-E activated by centrifugation for three days with ethanol solvent and among the amine-modified Gd-MOFs, 5d-S activated with ethanol for five days by the Soxhlet method have the best performance in terms of The specific surface area (qe=55.58 mg/g and SBET=23.92 m2/g, respectively), drug absorption, magnetic property of VSM are included. Also, compared to 5d-S, 3d-E has higher thermal stability, more drug absorption (its qmax is about 20 mg/g more) and double r1 coefficient. Among all the advantages of 3d-E compared to 5d-S, the results of the MTT test indicate that 3d-E nanoparticles show more toxicity than 5d-S in 24 hours. Following the detailed study of the properties of these two nanoparticles, we optimized the synthesis method of Gd-MOF nanoparticles to reduce the size of the particles. After examining different synthesis methods and optimizing different parameters of the selected method, the result showed that the use of PVP polymer in synthesis provides the best nanoparticles (PVP-HMTA) in terms of size and uniformity in diameter. Finally, the optimized PVP-HMTA nanoparticles were coated by PEG polymer to have the ability to pass through the BBB. The kinetics of quercetin drug release shows that it is released in two stages within 100 hours. The results of in vivo tests prove that the nanoparticle has the ability to pass through BBB and can create a significant difference in the contrast of MRI brain images before and after IP injection into rats. After the IP administration of quercetin nanocarrier, the recovery of the rat's spatial memory function can be seen in the Morris behavioral test. As a result, the designed nanoparticles show that in addition to controlling Alzheimer's disease, they play an important role as MRI contrast agent in early diagnosis of Alzheimer's disease
  9. Keywords:
  10. Alzheimer ; Blood Brain Barrier ; Metal-Organic Framework ; Magnetic Resonance Imagin (MRI) ; Morris Method ; Gadolinium Contrast Agent ; Polyethylen Glycol (PEG) ; Quercetin Drug

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