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The significance of platinum in the environment
Brestovská, Marta ; Holubová, Zuzana (referee) ; Sommer, Lumír (advisor)
This bachelor thesis deals with monitoring of individual platinum compounds in the environment (water, soil, air) and is also reviewing methods used for their analysis. The no less important determination of platinum in tissues and body fluids, when the platinum is used in form of a cisplatin as an anticancer drug, is also mentioned. Afterwards the anticancer drug itself or its derivatives and metabolites on the base of platinum complexes in clinical sample (urine, plasma) are determined. Mainly the ICP-AES, ICP-MS, ETA-AAS, HPLC methods are highlighted from the methods used for the determination of Pt. The on-line connection between some of these methods such as ICP-MS with HPLC or ICP-AES with HPLC seems to be useful. The spectrofotometric methods using organic and inorganic agents can also be used for the determination of platinum. These methods are mentioned here rather marginally, just for completeness. In terms of practical use they are difficultly reproducible and not very sensitive. The hydrolysis of platinum metals to form insoluble hydrated oxides makes also the determination difficult.
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Preparation of mitotic inhibitors in the form of nanotransporters
Meskařová, Veronika ; Indra, Radek (advisor) ; Hýsková, Veronika (referee)
Cancer is one of the most widespread diseases that every third person will encounter it. It is a disease arising from the sudden growth and rapid division of own cells. Despite progress in treatment, an effectiveness is not sufficient, and cancer is the second most common cause of death. In addition, the treatment is associated with several side effects. Currently nanomedicine uses nanomaterials for transport drugs in cancer treatment. It is possible to deliver the drug to the target site, but also to reduce the systemic toxicity of the drug by binding the drug to a suitable nanotransporter. This diploma thesis deals with seeking the appropriate mass ratio of antitumor drugs, colchicine and docetaxel, and the nanotransporter apoferritin. The aim was to find suitable in vitro conditions for high drugs encapsulation into the nanotransporter. Drugs encapsulation took place under active and passive conditions. Active encapsulation was under way on opening and closing nanotransporter by changing pH environment in test tube. Drugs were dissolved in DMSO or water with addition of HCl to charge the drug molecules and improve the binding of the drug into nanotransporter. As part of passive encapsulation, drugs were incubated in surroundings of urea or bivalent metal ions. Overall, it can be concluded that...
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The study of properties of anticancer drugs ellipticine, etoposide and doxorubicin in the forms of nanocarriers
Lengálová, Alžběta ; Stiborová, Marie (advisor) ; Martínková, Markéta (referee)
Currently available anticancer therapies are inadequate and spur demand for improved technologies. Among others, the utilization of nanocarriers for anticancer drug delivery has shown great potential in cancer treatment. Nanocarriers can improve the therapeutic efficiency of the drugs with minimization of the undesirable side effects. To evaluate potential application of this technology, two forms of nanocarriers have been studied: multi-walled carbon nanotubes (MWCNTs) and apoferritin. The aim of this study was to determine, whether given cytostatics (ellipticine, etoposide and doxorubicin) are bound to these nanotransporters and how are they released from them, especially depending on pH. Since the pH of the tumor cells is lower than the pH of healthy cells it would be preferred that the drugs would release from nanocarriers at the lower pH while at the physiological pH the release of the drug would be eliminated. The results found show that ellipticine is actually released from its MWCNT- and apoferrtin-encapsulated form at acidic pH (5.0), while at pH 7.4 its interaction with nanocarriers is stable. Ellipticine released from MWCNT is activated by microsomal enzymes to reactive metabolites (13- hydroxyellipticine and 12-hydroxyellipticine) forming DNA adducts. The results indicate that both...
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Metabolism of cabozantinib by enzymes of first phase of biotransformation
Jurečka, Tomáš ; Indra, Radek (advisor) ; Kubíčková, Božena (referee)
Cabozantinib is an anticancer drug that inhibit tyrosine kinases which allow signal pathways important for growth and development of tumors. It is used for treatment of medullary thyroid cancer, hepatocellular carcinoma and kidney cancer. The major enzymes of the first phase of biotransformation that metabolize cabozantinib are cytochromes P450. In this thesis it was studied metabolism of cabozantinib and cytochromes P450 that participated on this metabolism. Hepatic microsomes of rat, mouse and rabbit were used for studying metabolism of cabozantinib in this thesis. It was also focused on the impact of particular isoforms of cytochromes P450 on metabolism of cabozantinib in rat microsomes. Time dependence of cabozantinib conversion in hepatic rat microsomes was also studied. Enzyme kinetics of metabolism of cabozantinib in hepatic rat microsomes, as well as impact of cytochromes P450 inhibitors on the metabolism were included. Metabolites were analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. Formation of metabolites of cabozantinib increased over time to 30 minutes of incubation and with some others to 40 minutes of incubation. Up to five different metabolites were detected in experiments (M1, desmethyl cabozantinib, M3, monohydroxy cabozantinib and cabozantinib...
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The study of properties of anticancer drugs ellipticine, etoposide and doxorubicin in the forms of nanocarriers
Lengálová, Alžběta
Currently available anticancer therapies are inadequate and spur demand for improved technologies. Among others, the utilization of nanocarriers for anticancer drug delivery has shown great potential in cancer treatment. Nanocarriers can improve the therapeutic efficiency of the drugs with minimization of the undesirable side effects. To evaluate potential application of this technology, two forms of nanocarriers have been studied: multi-walled carbon nanotubes (MWCNTs) and apoferritin. The aim of this study was to determine, whether given cytostatics (ellipticine, etoposide and doxorubicin) are bound to these nanotransporters and how are they released from them, especially depending on pH. Since the pH of the tumor cells is lower than the pH of healthy cells it would be preferred that the drugs would release from nanocarriers at the lower pH while at the physiological pH the release of the drug would be eliminated. The results found show that ellipticine is actually released from its MWCNT- and apoferrtin-encapsulated form at acidic pH (5.0), while at pH 7.4 its interaction with nanocarriers is stable. Ellipticine released from MWCNT is activated by microsomal enzymes to reactive metabolites (13- hydroxyellipticine and 12-hydroxyellipticine) forming DNA adducts. The results indicate that both...
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Anticancer drugs in forms of nanoparticles and mechanisms potentiating their anticancer efficiency
Meskařová, Veronika ; Indra, Radek (advisor) ; Bělonožníková, Kateřina (referee)
Cancer has been one of the most common diseases of civilization for centuries. In the 18th century, some cancers were described and the first treatments were proposed. Currently, oncosurgery, chemotherapy, radiotherapy, immunotherapy and hormonal treatment are used to treat cancer. At the same time, efforts are being made to find new anticancer drugs that target tumor cells more selectively. Recently, nanomedicine has also started to be used. This bachelor thesis deals with minimizing the binding of the amount of cytostatic ellipticine to the surface of the nanotransporter apoferritin and achieving higher encapsulation efficiency. Two types of apoferritins at different weight ratios to ellipticine were studied. It has been found that by finding a suitable weight ratio of the two molecules, binding can be minimized, and encapsulation efficiency can be increased. When working with commercial apoferritin, there was a higher encapsulation and a lower binding of ellipticine to the surface at the weight ratio of 1:10. In contrast, when working with recombinant apoferritin, the encapsulation is higher and ellipticine binding are lower at the lower ratio of 1: 2,5. Key words: oncological diseases, anticancer drugs, nanomedicine, cytostatic, nanotransporter, ellipticine, apoferritin [IN CZECH]
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Preparation of anticancer drugs bound in apoferritin
Fürbacherová, Pavlína ; Indra, Radek (advisor) ; Koblihová, Jitka (referee)
Cancer is one of the most serious problems, which modern medicine faces. In recent years, nanotechnologies and their use in medicine, has developed greatly. The aim is to make drug administration more effective and help to improve treatment of cancer illnesses. Incorporation of chemical substance into a nanoparticle can solve the problem with low stability of the drug, and/or it help to eliminate side effects. Nanoparticle apoferritin, which was studied in this thesis, is a form of commonly occurring protein ferritin. Its structure contains cavity, that can be used for incorporation of drug. Its chemical structure (high temperature stability and stability at wide pH range, easy manipulation by changing pH) and its biocompatibility makes apoferritin a potentionally suitable transporter. Presented thesis studied apoferritin's ability to incorporate anticancer drug cabozantinib into its structure. Cabozantinib is tyrosine kinase inhibitor which is used for treatment of thyroid cancer, renal cell carcinoma and hepatocellular carcinoma. The effect of final pH to the formation of the complex of apoferritin with cabozantinib, and stability of this complex was also studied in this thesis. Considering the results we can say that apoferritin is able to encapsulate cabozantinib into its inner structure. As we...
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The study of properties of anticancer drugs ellipticine, etoposide and doxorubicin in the forms of nanocarriers
Lengálová, Alžběta
Currently available anticancer therapies are inadequate and spur demand for improved technologies. Among others, the utilization of nanocarriers for anticancer drug delivery has shown great potential in cancer treatment. Nanocarriers can improve the therapeutic efficiency of the drugs with minimization of the undesirable side effects. To evaluate potential application of this technology, two forms of nanocarriers have been studied: multi-walled carbon nanotubes (MWCNTs) and apoferritin. The aim of this study was to determine, whether given cytostatics (ellipticine, etoposide and doxorubicin) are bound to these nanotransporters and how are they released from them, especially depending on pH. Since the pH of the tumor cells is lower than the pH of healthy cells it would be preferred that the drugs would release from nanocarriers at the lower pH while at the physiological pH the release of the drug would be eliminated. The results found show that ellipticine is actually released from its MWCNT- and apoferrtin-encapsulated form at acidic pH (5.0), while at pH 7.4 its interaction with nanocarriers is stable. Ellipticine released from MWCNT is activated by microsomal enzymes to reactive metabolites (13- hydroxyellipticine and 12-hydroxyellipticine) forming DNA adducts. The results indicate that both...
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The study of properties of anticancer drugs ellipticine, etoposide and doxorubicin in the forms of nanocarriers
Lengálová, Alžběta ; Stiborová, Marie (advisor) ; Martínková, Markéta (referee)
Currently available anticancer therapies are inadequate and spur demand for improved technologies. Among others, the utilization of nanocarriers for anticancer drug delivery has shown great potential in cancer treatment. Nanocarriers can improve the therapeutic efficiency of the drugs with minimization of the undesirable side effects. To evaluate potential application of this technology, two forms of nanocarriers have been studied: multi-walled carbon nanotubes (MWCNTs) and apoferritin. The aim of this study was to determine, whether given cytostatics (ellipticine, etoposide and doxorubicin) are bound to these nanotransporters and how are they released from them, especially depending on pH. Since the pH of the tumor cells is lower than the pH of healthy cells it would be preferred that the drugs would release from nanocarriers at the lower pH while at the physiological pH the release of the drug would be eliminated. The results found show that ellipticine is actually released from its MWCNT- and apoferrtin-encapsulated form at acidic pH (5.0), while at pH 7.4 its interaction with nanocarriers is stable. Ellipticine released from MWCNT is activated by microsomal enzymes to reactive metabolites (13- hydroxyellipticine and 12-hydroxyellipticine) forming DNA adducts. The results indicate that both...
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