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Polymeric nanoparticles for poorly water soluble drugs delivery
Nekolová, Martina ; Holas, Ondřej (advisor) ; Smékalová, Monika (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Mentor: PharmDr. Ondřej Holas, Ph.D. Student: Martina Nekolová Title of thesis: Polymeric nanoparticles for poorly water-soluble drugs delivery Polymeric nanoparticles represent a modern drug form. One of the main advantages is influencing the pharmacokinetic properties of the administered substance - e.g. increasing solubility in water. They enable the targeted delivery of the drug to the affected tissue and this way minimize adverse effects. This could be of great benefit to the therapy of cancer or inflammatory diseases. Both the target tissue and the nanoparticles must have some specific properties. For particles, it is, for example, size and surface charge. The aim of this work was to prepare nanoparticles with a substance poorly soluble in water, represented by curcumin. The particles were prepared by the nanoprecipitation method with different types of poly(lactic-co-glycolic acid) (PLGA) copolymer. A 50:50 linear PLGA polymer and a branched PLGA A2 polymer were used. The prepared nanoparticles were compared on several parameters - particle size and polydispersity, encapsulation efficiency (EE), drug-loading capacity (DLC) and dissolution profile. PLGA 50:50 was found to provide...
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Adsorption of biologically active substances in colloidal solutions of aminoclay
Málková, Ivana ; Pekař, Miloslav (referee) ; Mravec, Filip (advisor)
This paper builds on a previous study of magnesium aminoclay and its interactions with biological compounds. The theoretical part deals with the research of the usage of aminoclay as a carrier in medical applications, the method of its formulation, the selection of biologically active compounds and a suitable method of varification. The experimental part deals with the synthesis of aminoclay, samples preparation and study of the adsorption behavior of the selected bioactive compounds under different conditions. The experimental part of the paper also includes varification of the suitability of the selected UV VIS spektrometry to determine the adsorption behavior of the biologically active compounds in colloidal aminoclay solutions.
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Curcumin in the treatment of traumatic spinal cord injury
Kloudová, Anna ; Machová Urdzíková, Lucia (advisor) ; Martončíková, Marcela (referee)
Spinal cord injury is a very significant clinical as well as social problem with extensive consequences, affecting the patient and also his/her family. Great efforts have been devoted to searching for an effective treatment, which would improve their situation. This thesis evaluated the effects of the natural compound curcumin on spinal cord injury using an experimental balloon compression model. Male Wistar rats were randomized into two groups following the lesion induction, namely vehicle- or curcumin-treated. The behavioral recovery was evaluated using a set of locomotor and sensory tests and a histological and imunohistochemical analysis was performed. The qPCR method was used to observe the expression of some genes related to regeneration and immune response. It was demonstrated that curcumin improved locomotor recovery after the spinal cord injury, particularly in the early stages. Morphometric analysis of the gray and white matter sparing didn't confirm any differences between the two groups. Nevertheless, the glial scar formation was significantly reduced around the central part of the lesion in the curcumin treated group and also the NF-κB activity was substantially inhibited. The gene expression analysis demontrated downregulation of Gfap and Rantes genes and upregulation of the Irf5 gene...
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Some aspects of molecular mechanisms of xenobiotics' hepatotoxicity and hepatoprotection : Modulatory roles of natural polyphenols
Lekic, Nataša ; Farghali, Hassan (advisor) ; Kršiak, Miloslav (referee) ; Brůha, Radan (referee)
Background & Aims: Oxidative stress and apoptosis are proposed mechanisms of cellular injury in studies of xenobiotic hepatotoxicity. The aim of this work is to find early signal markers of drug-induced injury of the liver by focusing on select antioxidant/oxidant and apoptotic genes. As well, to address the relationship between conventional liver dysfunction markers and the measured mRNA and protein expressions in the D-galactosamine/lipopolysaccharide and tert-butylhydroperoxide hepatotoxicity models. Furthermore, potential hepatoprotective capabilities of antioxidant polyphenols quercetin and curcumin were evaluated in relation to its modulation of the oxidative stress and apoptotic parameters in the given xenobiotic hepatotoxicity models. Methods: Biochemical markers testing the hepatic function included aminotransferases (ALT, AST) and bilirubin. Measurements of TBARS and conjugated dienes were used to assess lipoperoxidation. Plasma levels of catalase and reduced glutathione were used as indicators of the oxidative status of the cell. Real time PCR was used to analyse the mRNA expressions of the inducible nitric oxide synthase (NOS-2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD-1), glutathione peroxidase (Gpx-1), caspase 3 (Casp3), BH3 interacting domain death agonist (Bid) and Bcl-2...
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Disposable sensor of ammonium for intelligent packaging
Nentvichová, Aneta ; Kořínková, Radka (referee) ; Veselá, Mária (advisor)
This diploma thesis is focused on the problematic of the smart packaging and deals with the preparation of disposable ammonia sensors/indicators and the subsequent color measurement of prepared sensors/indicators using the CIE L* a* b* color space. The theoretical part of the diploma thesis focuses on active and intelligent packaging, using ammonia sensors/indicators. The emphasis is placed on the main components of the sensor/indicator, i.e., chitosan as a polymer and curcumin as a dye. The theoretical part also includes the problematic of meat degradation, which plays a very important role in this thesis. The experimental part was divided into two parts. The first part was to prepare layers that will respond in different colors based on the concentrations of ammonia. Prepared layers were sensitive to ammonia across all concentrations, and based on this result, ascorbic acid was applied to compositions to achieve a calibration retention of the selected amount of ammonia. The second minor part of the experiment was the application of selected layers to packages with real meat.
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Využití funkčních potravin v terapii nádorových onemocnění
Vašíčková, Kateřina
This diploma thesis with the name „Use of Functional Food in Cancer Therapy“ is focused on the study of the possibility of using nutraceuticals of functional food in cancer therapy. Literary part of this work deals with the topic of functional food and their positive effects on human body, especially in prevention and treatment of various type of diseases. One of the main topic is cancer and its treatment options. These days, research using nutraceuticals as a supplementary treatment or monotherapy modality of cancer is often the subject of research. In this work, the effect of nutraceutical curcumin, whose antitumor effects were tested in vitro in both monotherapy and supplementary breast cancer treatment, were investigated. As a supplementary treatment, curcumin was tested in synergy with the cytostatic doxorubicin. Biologically active molecules have been encapsulated into a cavity of protein nanocarrier apoferritin, which has been promoted to support molecule´s therapeutic effects while protecting non-transformed breast cells. The encapsulation efficiency was about 68–72 % for all applied molecules. Stability of encapsulated curcumin and doxorubicin complexes stored in aqueous medium at 4 °C and 20 °C for 48 hours was determined by monitoring the change in optical properties, the size and surface ζ-potential of the nanoparticles or premature drug release from the nanotransporter. In addition, a colloidal stability test have been confirmed the increased protection of biologically active molecules by the process of direct encapsulation. In solutions simulating the internal environment of the organism (blood plasma, cytoplasm, endosomes), the amount of the released molecules from the apoferritin cavity was monitored at 37 °C for 48 hours. The colloidal stability test determined the blood plasma behavior for 48 hours. The toxicity of the tested complexes against the tumor cell lines MDA-MB-231 and MDA-MB-468 was determined by several cell experiments. The HBL-100 cell line was consider as a control non-transformed cells. The research of this diploma thesis determined the oxidative stress of cell lines induced by prepared com-plexes and the rate of internalization of these formulations into cells. Biocompatibility was determined by monitoring protein corona formation on the surface of nanoparticles, activation of C3 complement component, genotoxic effects on healthy breast cell lines and hemolysis of erythrocytes in human blood.
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Properties of aminoclay complexes and biologically active substances
Dušek, Jakub ; Pekař, Miloslav (referee) ; Mravec, Filip (advisor)
This paper builds on previous research of aminoclay complexes in undergraduate studies. Theoretical part deals with study of current problems of aminoclay complexes with bioactive substances and the choice of substances for complexing with aminoclay. The experimental part consists of preparation of aminoclay complexes with selected bioactive agents at various concentrations. Verification of binding of bioactive agents to the aminoclay matrix was performed by Elemental Analysis (EA) and Fourier-transform infrared spectroscopy (FT-IR). For finding of the bound amount of bioactive substance were used the Ultra Performance Liquid Chromatography (UPLC®) and analysis of the cytotoxic properties of the formed complexes by used by the MTT assay. The main motivation of this study is to create new complexes with improved characteristics that would replace existing forms of substances used in pharmaceutical and biomedical applications.
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Curcumin in the treatment of traumatic spinal cord injury
Kloudová, Anna ; Machová Urdzíková, Lucia (advisor) ; Martončíková, Marcela (referee)
Spinal cord injury is a very significant clinical as well as social problem with extensive consequences, affecting the patient and also his/her family. Great efforts have been devoted to searching for an effective treatment, which would improve their situation. This thesis evaluated the effects of the natural compound curcumin on spinal cord injury using an experimental balloon compression model. Male Wistar rats were randomized into two groups following the lesion induction, namely vehicle- or curcumin-treated. The behavioral recovery was evaluated using a set of locomotor and sensory tests and a histological and imunohistochemical analysis was performed. The qPCR method was used to observe the expression of some genes related to regeneration and immune response. It was demonstrated that curcumin improved locomotor recovery after the spinal cord injury, particularly in the early stages. Morphometric analysis of the gray and white matter sparing didn't confirm any differences between the two groups. Nevertheless, the glial scar formation was significantly reduced around the central part of the lesion in the curcumin treated group and also the NF-κB activity was substantially inhibited. The gene expression analysis demontrated downregulation of Gfap and Rantes genes and upregulation of the Irf5 gene...
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Some aspects of molecular mechanisms of xenobiotics' hepatotoxicity and hepatoprotection : Modulatory roles of natural polyphenols
Lekic, Nataša ; Farghali, Hassan (advisor) ; Kršiak, Miloslav (referee) ; Brůha, Radan (referee)
Background & Aims: Oxidative stress and apoptosis are proposed mechanisms of cellular injury in studies of xenobiotic hepatotoxicity. The aim of this work is to find early signal markers of drug-induced injury of the liver by focusing on select antioxidant/oxidant and apoptotic genes. As well, to address the relationship between conventional liver dysfunction markers and the measured mRNA and protein expressions in the D-galactosamine/lipopolysaccharide and tert-butylhydroperoxide hepatotoxicity models. Furthermore, potential hepatoprotective capabilities of antioxidant polyphenols quercetin and curcumin were evaluated in relation to its modulation of the oxidative stress and apoptotic parameters in the given xenobiotic hepatotoxicity models. Methods: Biochemical markers testing the hepatic function included aminotransferases (ALT, AST) and bilirubin. Measurements of TBARS and conjugated dienes were used to assess lipoperoxidation. Plasma levels of catalase and reduced glutathione were used as indicators of the oxidative status of the cell. Real time PCR was used to analyse the mRNA expressions of the inducible nitric oxide synthase (NOS-2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD-1), glutathione peroxidase (Gpx-1), caspase 3 (Casp3), BH3 interacting domain death agonist (Bid) and Bcl-2...
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Use of some exotic natural extracts in cosmetics
Phan, Huong Tra ; Němcová, Andrea (referee) ; Márová, Ivana (advisor)
The objective of this bachelor thesis was a general characterization of the antioxidant effect of exotic plants and their extracts. The selected plants were Zingiber officinale, Turmeric longa and Momordica charantia. Theoretical part focuses on antioxidative properties, genereal characteristics of selected plants and description of the methods applied in the experimental part. In the experimental part, content of the antioxidant activity, polyphenols, flavonoids were characterized by spectrophotometry. Major active ingredient (curcumin, gingerol) and other substances like tocopherol were determined by HPLC/UV-VIS. Finally, potential practical use of these active substances in the field of cosmetics including skin hydration measurement was tested.
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