Synthesis and identification of Ho-POSS complex with capping application in medical devices

Number of pages: 128 File Format: word File Code: 31899
Year: 2012 University Degree: Master's degree Category: Industrial Engineering
  • Part of the Content
  • Contents & Resources
  • Summary of Synthesis and identification of Ho-POSS complex with capping application in medical devices

    Master's thesis in the field of polymer science and technology

    Abstract:

    Today, cancer is one of the most important concerns of the medical world for which no definitive treatment has been found yet. Radiation therapy is one of the methods used to control and reduce the complications of cancer. Brachytherapy is one of these radiation therapy methods in which the radiation source is placed near the cancerous tissue by several methods. Usually, metals such as yttrium, rhenium, helium and non-metals such as phosphorus are used as a source of radiation for this application after being activated with a neutron beam. In recent years, helium radioactive isotope has been very much considered for brachytherapy due to its short half-life and having the characteristics required for brachytherapy, including the optimal amount of energy emitted by the beam. One such technique is placing the radiation source in a polymer substrate (polymer composite preparation). However, usually helium metal (as a radiation source) is used in the form of metal oxide, metal salts or even in the form of metal powder. These inorganic compounds are not well distributed in polymer substrates due to the relatively high surface energy difference. For this reason, an attempt was made to overcome this problem by synthesizing a bulk complex of helium metal with a suitable ligand. It is expected that the selection of suitable ligands with organic substitutions will help to improve the diffusion and trapping of the metal-containing complex in the polymer substrate. In this research, the polyhedral oligomeric silsesquioxane-triol (POSS) ligand with an incomplete cage structure was used to form a complex with helium metal. The bulky POSS ligand with the general formula Rn Sin O1.5n is a silicon cage, and the organic R groups connected to silicon in the corners of the silicon cage give this ligand an organic-inorganic hybrid property. Having this feature helps to better distribute the complex in the polymer substrate. In addition, this ligand with the known biocompatibility of the silicon cage can simultaneously increase the biocompatibility of the brachytherapy system and its resistance to radiation. So far, the complexation of POSS with various metals of the periodic table (main group metals, transition metals and rare metals) has been reported. However, there is no report on its complex synthesis with helium metal. In this research, three known methods were used for the synthesis of Ho-POSS complex. In the first method for the synthesis of Ho-POSS complex, using sodium propanoate and helium nitrate salt, helium propanoate complex was synthesized, and then, by adding POSS, the displacement of the ligand was done. The results of FTIR and EDX confirmed the synthesis.  However, the NMR results showed that POSS did not enter the reaction with its full capacity. In the second method, the synthesis of Ho-POSS complex was performed in the presence of triethylamine (as a Lewis base) and in THF solvent, and the results of FTIR spectroscopy showed that this method is not suitable for the synthesis of Ho-POSS. In the third method, lithium base (trimethylsilylamide) was used for the synthesis of Ho-POSS complex. The results of FTIR spectroscopy of the product confirmed the correctness of the synthesis of this intermediate. FTIR, NMR and EDX were used to identify the final complex and its thermal behavior was studied using TGA method. The results of the mentioned tests confirmed the formation of the complex. Using fluorescence and photoluminescence spectrometers, the emission capability of the complex was further investigated with UV light wavelength excitation. The results of fluorescence spectroscopy with 330 nm excitation light showed emission at 470 nm wavelength. This publication was confirmed in the photoluminescence device exactly at the wavelength of 470 nm. In UV-Vis spectroscopy, a red shift from the wavelength of 221 nm to 269 nm was observed. These changes are caused by changes in the structure of POSS and the formation of a new structure. Finally, it can be said that this synthesis method provided a higher efficiency than the previous two syntheses. Finally, the complex composite (wt% 5) with polyurethane based on polycaprolactone, hexamethylene diisocyanate and 1,4-butane DL was prepared and sent for cytotoxicity test. The result of the test showed that this complex does not show cytotoxicity. Introduction

    Cancer treatment methods are mainly divided into three categories: surgery, chemotherapy and radiotherapy.

     

    1          Chapter One: Introduction

    Cancer treatment methods are mainly divided into three categories: surgery, chemotherapy and radiotherapy. The mentioned methods can be used independently or in combination. Radiotherapy methods [1] are divided into two branches: remote radiotherapy [2] and close radiotherapy [3]. Chemotherapy drugs are prescribed to prevent the severity of the disease and in cases where the cancer has spread in the body. The side effects of chemotherapy include nausea and vomiting, loss of head and eyebrow hair, decrease in the number of white blood cells, weak immune system, infection, pain, dry mouth, osteoporosis, anemia, and decrease in the number of red blood cells, which may cause fatigue, dizziness, and feeling cold in the patient. Diarrhea, constipation, stiffness and dryness of the joints are other side effects of chemotherapy. or it is done before the cancerous tumor surgery. In this method, the cells of the treated area (target tissue) are destroyed and their growth and division is impossible. The aim of radiotherapy is to destroy the cancer cells as much as possible while minimizing the damage to the healthy tissues. In some patients, the goal of the treatment is to completely destroy the tumor and in some cases to reduce its symptoms If not, more extensive treatment methods such as radiotherapy are performed. An example of a device used for this purpose can be seen in Figure 1-1. they bring In each patient, a special treatment is designed to protect healthy tissues (as much as possible). Almost half of cancer patients receive radiotherapy. Radiotherapy may be used to treat all types of solid tumors including brain, breast, cervix, larynx, lung, pancreas, prostate, skin, spinal cord, stomach, uterus and lymphoma (lymphatic system tumor) and some benign tumors. The amount of dose used for radiotherapy depends on the type of tumor, tissue or organs affected. In some cases, radiation to non-cancerous areas is also done in order to prevent the regrowth of cancer cells, which is called preventive radiotherapy [5]. Radiotherapy can also help reduce the symptoms of the disease, such as pain caused by the spread of cancer to bones or other body tissues, which is called palliative radiotherapy [6]. In remote radiotherapy or teletherapy, the patient is exposed to radiation, which means that the radiation is directed from a radioactive source and from several different angles from outside the body to the tumor. This procedure is completely painless and lasts for 7 to 8 weeks. But the patient complains of side effects such as anal irritation, diarrhea and extreme fatigue caused by radiation. The effects of radiation may appear in the form of skin reactions including inflammation, itching, burning, discharge or scaling of the skin. Nausea, vomiting, anorexia and vascular and respiratory damage can be other side effects of radiotherapy. Also, radiotherapy may suppress the body's hematopoietic system, reduce white blood cells, weaken the body's immune system, and ultimately cause infection. Teletherapy is used to treat all types of cancer, including bladder, brain, breast, anus, pancreas, stomach, cervix, larynx, lung, prostate, and uterus.

    On the other hand, brachytherapy is a method that uses radioisotopes that are placed near cancer cells to deliver a large amount of radiation directly to the malignant lesion to weaken or destroy the cancer cells. The emission caused by appropriate radioisotopes should be focused exactly on the target lesion. With this treatment method, a high radiation dose can be delivered to the tumor in a concentrated manner so that a rapid drop in the dose can be observed in the healthy tissues around the tumor.

  • Contents & References of Synthesis and identification of Ho-POSS complex with capping application in medical devices

    List:

    Chapter One: Introduction. 1

    1-1 Chemotherapy. 1

    1-2 Radiotherapy. 3

    1-3 Advantages and disadvantages of radiotherapy and brachytherapy. 5

    1-4     Radiation and the mechanism of conversion of radioactive elements. 6

    1-5 Energy sources used in brachytherapy. 8

    1-6 Brachytherapy with helium complex. 9

    1-7 The necessity of choosing the right ligand for helium metal in the application of brachytherapy. 10

    1-7-1 polyhedral oligomeric silsesquioxane (POSS). 10

    1-8 POSS nanocomposites. 12

    1-9 Chemistry of lanthanide metals. 14

    1-10 complexes with POSS ligand. 17

    Chapter Two: An overview of the studies done. 18

    1-2 Silesian chemistry of oxane. 18

    2-2 Synthesis of Ho-POSS complex using alkoxide, amine and alkyl metal (first method) 22

    2-3 Synthesis of metal-POSS complex in the presence of amine compound. 25

    2-4 Side reactions in the method of using amine for metal-POSS complex. 28

    2-5    Synthesis of POSS-metal complex using lithium bis(trimethylsilylamide) (third method) 28

    2-6    F group metal complexes with POSS. 30

    The third chapter: Experimental part. 36

    3-1     Materials. 36

    3-2 Synthesis of POSS-Ho. 37

    3-2-1       Synthesis of complex 1 using metal alkoxide. 38

    3-2-2       Synthesis of complex 2 (using helium chloride salt in the presence of Lewis amino base). 39

    3-2-3 Synthesis of complex 3 (using helium chloride in the presence of lithium trimethylsilylamide) 39

    3-3 Polyurethane synthesis. 40

    3-4            Identifications. 40

    3-4-1 Centrifuge. 40

    3-4-2       Differential scanning calorimetry (DSC). 40

    3-4-3 Freeze dryer. 41

    3-4-4       Optical microscopy. 41

    3-4-5 Fourier transform infrared spectroscopy (FTIR). 41

    3-4-6       Thermogravimetric analysis (TGA). 42

    3-4-5       Total Attenuated Reflectance - Surface Infrared Spectroscopy (ATR-FTIR) test. 42

    3-4-6       EDX. 43

    3-4-7 NMR. 43

    3-4-8      Ultraviolet (UV) light spectroscopy. 43

    3-4-9       Thin layer chromatography. 44

    3-4-10 Fluorescence spectroscopy. 44

    3-4-11 Photoluminescence (PL). 45

    3-5 Biocompatibility review. 45

    Chapter Four: Results and discussion. 46

    4-1         Preparation of raw materials. 46

    4-1-1 FTIR spectroscopy of pure POSS. 46

    4-1-2       Drying helium nitrate. 47

    4-1-3 ATR. 53

    4-2 Complex synthesis. 54

    4-2-1 The results of complex synthesis by the first method (complex 1). 55

    4-3 POSS-Ho complex purification methods. 56

    4-3-1       EDX. 57

    4-4 Analysis of complex 1. 58

    4-4-1 Analysis of complex 1 by FTIR. 58

    4-4-1 Identification of complex 1 by nuclear magnetic resonance spectroscopy (NMR). 61

    4-5 Complex synthesized in the presence of amine (complex 2). 73

    4-5-1 Identification of complex 2 by FTIR method. 73

    4-6            Identification of complex 3. 74

    4-6-1 Identification of complex 3 by FTIR method. 76

    4-6-2 EDX related to complex 3. 79

    4-6-3 Identification of complex 3 by NMR spectroscopy. 79

    4-6-4 Checking the thermal behavior of the complex with TGA test. 81

    4-7           Examining the behavior of the complex in the UV-Vis range. 83

    4-7-1       Thin layer chromatography (TLC). 84

    4-7-2      UV spectroscopy. 85

    4-7-3 Fluorescence spectroscopy (fluorimetry). 87

    4-7-4       Photoluminescence. 89

    4-8     Biocompatibility of the complex. 92

    4-9 Investigating the possibility of forming POSS micelles in the solvents used in the reaction. 93

    4-10 Polyurethane identification with FTIR. 94

    4-10-1     TGA Polyurethane. 97

    4-10-2 Examining the mechanical and thermal properties of polyurethane by DSC method. 98

    4-10-3     Investigating the effect of using POSS for spreading helium in polyurethane substrate. 99

    Chapter Five: Conclusion. 100

     

    Source:

     

    [1] Cutrer M., Terwilliger R., Winch F., Zhang J., W. Higgins, T.Ellard, , D. Bossi, "Brachytherapy apparatus", United States Patent: 8137256, 2012

    [2] Pedersen L., Barber J., Crouther R., Femrite D., Henderson S., "Brachytherapy medical devices", United States Patent: 6639237, 2003

    ]3[ Ghafourian H., Ghahrani M.,"Design and manufacture of phosphorus-32 intravascular brachytherapy device for coronary artery irradiation", Nuclear Science and Technology Magazine, 29, 1-5, 1382

    [4] Chan A., Oelsner S., Simpson T., "Radioactively coated devices", United States Patent: 6394945, 2002.

    [5] White J., Stephens D., Govil A., Bergman J., Griffith N., Millage K., "Expandable brachytherapy device", United States Patent: 749781920, 2009.

    [6] Schaart D., "Method for manufacturing radioactive brachytherapy source material, brachytherapy source material and encapsulated radioactive brachytherapy source", United States Patent: 7311655, 2007

    ]7[Javaheri Deha F. , "Preparation of on-site drug delivery system based on degradable unsaturated polyesters containing radiopharmaceutical Holmium with brachytherapy application, Islamic Azad University, Department of Medicine, 2008

    ]8 [Alipour A. Discussions of radiopharmacy, University of Isfahan, 1368

    ]9 [Rais Ali G., Sadeghi M., Atainia V., "Determining the dosimetric parameters of the second Pd-103 seed model made in the Agricultural, Medical and Industrial Research Institute", Iranian Journal of Medical Physics, 1, 23-9-9, 1387

    ]10 [Soleimianian A., Alipoura., Ghafouri M., "Standard calibration of cesium-137 sources used in brachytherapy." Journal of Nuclear Sciences and Technologies, 34, 53-56, 1384

    ]11 [Pourbigi H., Shibani S., Ghafourian H., "Renium-186 radioisotope dosimetry for use in intravascular brachytherapy to reduce the recurrence of vascular stenosis," Journal of Nuclear Sciences and Technologies , 37, 10-16, 1385.

    ]12[ Rais Ali G., Sadeghi M., Atainia V., "Determining the dosimetry parameters of the second Pd-103 seed model made in the Agricultural, Medical and Industrial Research Institute", Iranian Journal of Medical Physics, 1, 9-23, 1387.

    ] 13 [Mohamadim., Garhami A. "Production of Iridium-192 in the Atomic Energy Organization of Iran for Brachytherapy" Scientific Journal of Hamedan University of Medical Sciences, 9, 57-60, 1381.

    [14] Nijsen J.F.W., "Microsphere comprising an organic lanthanide metal complex" United States Patent, 20110038793A1, 2001

    [15] Bult W., Leeuw H., Steinebach O. M., Bom M. J., Nijsen J. F. W., "Radioactive Holmium Acetylacetonate Microspheres for Interstitial Microbrachytherapy An In Vitro and In Vivo", Pharm. Res., 29, 827-836, 2012

    [16] Wu J., Mather P. T., “POSS polymer: Physical properties and biomaterials applications”, Journal of Macromolecular Science, part C, polymer review, 49, 25-63, 2009

    [17] Madbouly S. A., Otaigbe J. U., Recent advances in synthesis, characterization and rheological properties of polyurethanes and POSS/polyurethane nanocomposites dispersions and films", Progress in Polymer Science, 34,1283-1332, 2009

    [18] Zhou Z., Cui L., Zhang Y., Yin N., "Preparation and properties of POSS grafted polypropylene By reactive blending", Eur. Poly. J., 44, 3057-3066, 2008

    [19] Fina A., Tabuani D., Camino G., "polypropylene-polysilsesquioxane blends", Eur. Polym. J., 46, 14-23, 2010

    [20] liu L., Tian M., Zhang W., “Crystalization and morphology study of polyhedral oligomeric silsesquioxane (POSS)/polysiloxane elastomer composites prepared by melt blending”, polymer, 48, 3201-3212, 2007

    [21] Pracella M., Pancrazi C., BartczakZ. "Reactive mixing of polypropylene /POSS nanocomposite crystallization, morphology and thermal properties", 17th International Conference on Composite Materials, 2009

    [22] Kim B.S., Mather P. T, "Amphiphilic telechelic sincorporating polyhedral oligosilsesquioxame", Macromolecules, 35, 8378-8384, 2002

    [23]Mitsuishi M., Zhao F., Kim Y., Watanabe A., Miyashita T., “Bulk and Surface Assembly of Branched Amphiphilic Polyhedral Oligomer Silsesquioxane Compounds”, Chem.Mat, 20, 4310-4316, 2008

    [24] Kannana R. Y., Salacinski H. J., Edirisinghe M. J., Hamiltonc. G., Seifaliani A. M.

Synthesis and identification of Ho-POSS complex with capping application in medical devices