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Native hyaluronan as a delivery system for hydrophobic drugs
Černá, Eva ; Mravec, Filip (referee) ; Pekař, Miloslav (advisor)
The aim of this paper is to discover whether it is possible to use the native form of hyaluronic acid as a hydrophobic drug carrier for a targeted distribution in the body. In its structure, hyaluronic acid is a linear high molecular weight biopolysaccharide which is found in most living organisms. Hyaluronan is involved in many physiological processes and therefore is essential for the functionality of the human body. It is in most tissues of the human body, high concentration is in the skin, the vitreous body and is also observed in cancer cells that contain several receptors for hyaluronan. These receptors include CD44 and RHAMM. The interaction of the hyaluronic acid delivery system and the hydrophobic medicinal with these receptors could ensure a free passage for drugs to the affected tissue, where the release of the drug would destroy the affected cells. The drug would directly target the damaged tissue and did not burden the rest of the body like the cytotoxic agents do. In this paper the native form of hyaluronic acid, which we normally find in the human organism, was chosen as the carrier. Its properties do not stand above other carrier systems, but its biocompatibility and biodegradability in the body greatly exceed them. High molecular weight hyaluronic acid was used as a carrier and the hydrophobic dye sudan red G, a substance of similar properties, was used instead of a hydrophobic drug.
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Hyaluronan for targeted drug delivery
Ureš, Tomáš ; Vávrová, Milada (referee) ; Pekař, Miloslav (advisor)
Hyaluronic acid (hyaluronan, HA) is a linear polysaccharide formed from disacharide units containing N-acetyl-D-glucosamine and glucuronic acid. HA is present in almost all biological fluids and tissues. In many cancer cells there is an upregulation of CD44, a receptor that binds HA. The receptor CD44 collocates hyaluronan in the special way. The bioconjugates built-up from the cytotoxic substances and hyaluronan are called prodrugs. The prodrugs can be used for targeted drug delivery system. Their main advantage is there is no need to medicine so high doses of pharmaceuticals and their adverse side effects are minimized. Hyaluronan can be used as well as the intra-articulation injection by osteoarthritis. HA is also used as the nutrition of joints, by treatment for diverse dermatic lesions, the repair of scars and it can be the ingredient of eye drops and nasal sprays. The cosmetic manufactures add HA into anti-wrinkle creams and anti-aging care.
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Native hyaluronan as delivery agent for hydrophobic molecules
Michalicová, Petra ; Márová, Ivana (referee) ; Pekař, Miloslav (advisor)
Hyaluronan is a chemical, which can be qualified as essential for vertebrates. It is a part of the extracellular matrix in most of tissues and also a major component of some other tissues. Besides of the mechanical functions this compound is important for many biological processes such as growth of tumor cells. The objective of this thesis was development of carrier systems containing native hyaluronan and hydrophobic drugs. For purposes of this work fluorescence probes (pyrene, prodan, perylene, DPH, mereocynine 540) instead of drugs were used. By using further mentioned sophisticated methods the properties of these systems were studied. The systems were prepared by freeze-drying. The effect of freeze-drying on support of interactions was observed by fluorescence spectrometry (steady-state and time-resolved). The stability of freeze-dried systems was determined by zeta potential, which was measured by electrophoretic light scattering. Cakes obtained by freeze-drying were analyzed by several methods. First one was effluence gas chromatography connected with FT-IR spectrometry. In this method the present of tertiary butyl alcohol in product was observed. The cakes were also analyzed by scanning electron microscopy, which can provide the information about the surface and elemental constitution of the material. The results of this work can shed light on the area of developing of drugs with targeted distribution of active compound.
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Solubilization in sonographic systems
Überall, Martin ; Klučáková, Martina (referee) ; Mravec, Filip (advisor)
The aim of this thesis was to determine the solubilizing capacity of microbubbles based on SonoVue®, and phospholipids SonoVue® is made of, by using the UV-VIS spectrophotometry. The concentrations of solubilized substances within these systems was further determined. In particular, the properties of natrium dipalmitoylphosphatidylglycerole and distearoyl¬phosphatidylcholine were investigated. The microbubbles were produced using these phospholipids with the addition of polyethyleneglycol and palmitic acid. The solubilizing capacity was determined using hydrophobic solutes Sudan Red G, Oil Red O, 4-Di-2-Asp and Nile Red in order to obtain a model system of solubilized drugs or other hydrophobic substances. The behavior of solutes in phospholipids and our prepared microbubbles were examined in a moderately polar medium – physiological saline solution (0.15 M NaCl). The vizualization of prepared microbubbles was performed using optical and fluorescence microscopy. 4-Di-2-Asp, as a fluorescence probe, was not suitable for microbubble vizualization. The size of microbubbles that were produced during the experiment was almost the same as the size of microbubbles of commercially made SonoVue®. The concentration of solubilized hydrophobic solutes inside the liposomes of phospholipids ranged from tens to hundreds of micromoles per liter. With increasing concentration of phospholipids the concentration of solubilized solutes also increased. The results of this experiment can be used for further research focused on the solubilization of drugs in microbubbles, and contrast agents which are used in ultrasonography.
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Native hyaluronan as a delivery system for hydrophobic drugs
Černá, Eva ; Mravec, Filip (referee) ; Pekař, Miloslav (advisor)
The aim of this paper is to discover whether it is possible to use the native form of hyaluronic acid as a hydrophobic drug carrier for a targeted distribution in the body. In its structure, hyaluronic acid is a linear high molecular weight biopolysaccharide which is found in most living organisms. Hyaluronan is involved in many physiological processes and therefore is essential for the functionality of the human body. It is in most tissues of the human body, high concentration is in the skin, the vitreous body and is also observed in cancer cells that contain several receptors for hyaluronan. These receptors include CD44 and RHAMM. The interaction of the hyaluronic acid delivery system and the hydrophobic medicinal with these receptors could ensure a free passage for drugs to the affected tissue, where the release of the drug would destroy the affected cells. The drug would directly target the damaged tissue and did not burden the rest of the body like the cytotoxic agents do. In this paper the native form of hyaluronic acid, which we normally find in the human organism, was chosen as the carrier. Its properties do not stand above other carrier systems, but its biocompatibility and biodegradability in the body greatly exceed them. High molecular weight hyaluronic acid was used as a carrier and the hydrophobic dye sudan red G, a substance of similar properties, was used instead of a hydrophobic drug.
|
|
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Solubilization in sonographic systems
Überall, Martin ; Klučáková, Martina (referee) ; Mravec, Filip (advisor)
The aim of this thesis was to determine the solubilizing capacity of microbubbles based on SonoVue®, and phospholipids SonoVue® is made of, by using the UV-VIS spectrophotometry. The concentrations of solubilized substances within these systems was further determined. In particular, the properties of natrium dipalmitoylphosphatidylglycerole and distearoyl¬phosphatidylcholine were investigated. The microbubbles were produced using these phospholipids with the addition of polyethyleneglycol and palmitic acid. The solubilizing capacity was determined using hydrophobic solutes Sudan Red G, Oil Red O, 4-Di-2-Asp and Nile Red in order to obtain a model system of solubilized drugs or other hydrophobic substances. The behavior of solutes in phospholipids and our prepared microbubbles were examined in a moderately polar medium – physiological saline solution (0.15 M NaCl). The vizualization of prepared microbubbles was performed using optical and fluorescence microscopy. 4-Di-2-Asp, as a fluorescence probe, was not suitable for microbubble vizualization. The size of microbubbles that were produced during the experiment was almost the same as the size of microbubbles of commercially made SonoVue®. The concentration of solubilized hydrophobic solutes inside the liposomes of phospholipids ranged from tens to hundreds of micromoles per liter. With increasing concentration of phospholipids the concentration of solubilized solutes also increased. The results of this experiment can be used for further research focused on the solubilization of drugs in microbubbles, and contrast agents which are used in ultrasonography.
|
|
|
Native hyaluronan as delivery agent for hydrophobic molecules
Michalicová, Petra ; Márová, Ivana (referee) ; Pekař, Miloslav (advisor)
Hyaluronan is a chemical, which can be qualified as essential for vertebrates. It is a part of the extracellular matrix in most of tissues and also a major component of some other tissues. Besides of the mechanical functions this compound is important for many biological processes such as growth of tumor cells. The objective of this thesis was development of carrier systems containing native hyaluronan and hydrophobic drugs. For purposes of this work fluorescence probes (pyrene, prodan, perylene, DPH, mereocynine 540) instead of drugs were used. By using further mentioned sophisticated methods the properties of these systems were studied. The systems were prepared by freeze-drying. The effect of freeze-drying on support of interactions was observed by fluorescence spectrometry (steady-state and time-resolved). The stability of freeze-dried systems was determined by zeta potential, which was measured by electrophoretic light scattering. Cakes obtained by freeze-drying were analyzed by several methods. First one was effluence gas chromatography connected with FT-IR spectrometry. In this method the present of tertiary butyl alcohol in product was observed. The cakes were also analyzed by scanning electron microscopy, which can provide the information about the surface and elemental constitution of the material. The results of this work can shed light on the area of developing of drugs with targeted distribution of active compound.
|
|
|
Hyaluronan for targeted drug delivery
Ureš, Tomáš ; Vávrová, Milada (referee) ; Pekař, Miloslav (advisor)
Hyaluronic acid (hyaluronan, HA) is a linear polysaccharide formed from disacharide units containing N-acetyl-D-glucosamine and glucuronic acid. HA is present in almost all biological fluids and tissues. In many cancer cells there is an upregulation of CD44, a receptor that binds HA. The receptor CD44 collocates hyaluronan in the special way. The bioconjugates built-up from the cytotoxic substances and hyaluronan are called prodrugs. The prodrugs can be used for targeted drug delivery system. Their main advantage is there is no need to medicine so high doses of pharmaceuticals and their adverse side effects are minimized. Hyaluronan can be used as well as the intra-articulation injection by osteoarthritis. HA is also used as the nutrition of joints, by treatment for diverse dermatic lesions, the repair of scars and it can be the ingredient of eye drops and nasal sprays. The cosmetic manufactures add HA into anti-wrinkle creams and anti-aging care.
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