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Standardization of a method for in vitro assessment of copper chelation
Sedlářová, Lucie ; Mladěnka, Přemysl (advisor) ; Ramos Mandíková, Jana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Lucie Sedlářová Supervisor: Dr. Přemysl Mladěnka, Ph.D. Title of thesis: Standardization of method for in vitro assessment of copper chelation. Cooper is a trace element, which is essential for many biochemical processes in the human body. Disruption of copper homeostasis can cause a variety of diseases. There are primarily two hereditary diseases associated with copper dyshomeostasis: Wilson's disease, which is linked with the excess of copper in the liver and other tissues, and Menkes disease, which is associated with a lack of systemic copper. In addition, local disturbances of copper play a role also in other diseases (neurodegenerative diseases, tumors, myocardial infarction). The main objective of this experimental work was the standardization of a simple but accurate method for rapid screening of copper chelators, which could be applied for the therapy of systemic or local copper excess in the future. The methodology is based on the spectrophotometric determination of copper in microplates using appropriate indicators, bathocuproindisulfonic acid disodium salt (BCS) and hematoxylin. This thesis has shown that the BCS methodology is able to determine chelation of cupric as...
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Chelating polymers for the therapy of Wilson's disease
Mattová, Jana ; Poučková, Pavla (advisor) ; Sedláková, Zdeňka (referee) ; Vávrová, Jiřina (referee)
Wilson's disease is a hereditary disorder of copper metabolism, which causes copper accumulation in organism, especially in the liver, kidneys and brain. Current treatment is based on using low-molecular weight copper chelators and high doses of zinc salts. Unfortunately, they can induce some severe side effects due to systemic action. The aim of this thesis is to improve the treatment of Wilson's disease by using of polymeric drug delivery systems. The size of polymer particles in tens of microns should provide non-resorbability of the drug after oral administration. Synthetic microparticles of poly(glycidyl methacrylate-co- ethylene dimethacrylate), natural microcrystalline cellulose and cross-linked chitosan were used as polymer matrices. N,N-di(2-pyridylmethyl)amine, triethylenetetraamine and 8-hydroxyquinoline were selected as specific copper chelators, which can complex copper cations with high efficiency. The principle of the proposed treatment is that the polymeric carrier-bound chelator complex copper directly from the food in digestive tract of the organism. Because of non-resorbability, the entire complex should be eliminated from the body together with stools. This virtually eliminates systemic side effects. The ability of adsorption of copper and the stability of polymer complex under...
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