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Modeling of biologically relevant lipid multilayers in the context of drug delivery
Saija, Maria Chiara ; Cwiklik, Lukasz (advisor) ; Szczęsna-Iskander, Dorota (referee) ; Heyda, Jan (referee)
Understanding the topical drug delivery at basic physico-chemical and biophysical levels is still challenging. One of the main reasons is the specificity of the processes involved, depending on the delivery target. The tear film lipid layer plays a vital role in ocular health and serves as a target for topical ophthalmic drug delivery. This doctoral thesis investigates two topics related to topical eye delivery, including a case study of drug delivery systems and their major components in the tear film lipid layer, and the effect of a lipid modification on a lipid-associate peptide as a potential drug. This research is conducted by using molecular dynamics simulations, which are comple- mented by various experimental techniques. The research about the drug delivery systems is threefold: the first objective is to study the impact of commonly used preservatives on the tear film lipid layer; the second one is to explore the influence of the latanoprost drug on the tear lipids; the third one is to investigate different drug delivery systems containing latanoprost drug and their interaction with the lipid layer in the tears. These studies are conducted by combining molecular dynamics simulations and the experiments involving the Langmuir-type lipids film. The key findings of this research have practical...
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Simulation of the interaction of steroid allosteric modulators of NMDA receptors with membrane
Riedlová, Kamila ; Konopásek, Ivo (advisor) ; Novák, Josef (referee)
Molecular dynamics (MD) method allows the real-time monitoring of the system composed of molecules and atoms, such as phospholipid bilayer or biomolecule. Applications of MD are very common in drug design where the real experimental procedures could be much more financially- and time-consuming or even impossible. The aim of this project is to explain the applications and advantages of MD method in case of studies of lipid membranes, with a special emphasis on a study od neurosteriod behaviour in lipid bilayer. Properly designed and synthesized neurosteroids could be used for the treatment of the serious neurological diseases. This work also included the experimental data obtained by MD simulations for two neurosteroids - pregnanolone glutamate and pregnanolone sulphate. Behaviour of this molecules in model membranes was observed and analyzed by MD simulations. Key words: molecular dynamics simulation, model membrane, lipid bilayer, NMDA receptor, neurosteroids, pregnanolone glutamate, pregnanolone sulfate
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The effects of ions and oxidation on hydration and mobility of model lipid membranes.
Vojtíšková, Alžběta ; Jurkiewicz, Piotr (advisor) ; Michl, Martin (referee)
The presented thesis is a continuation of the bachelor work, in which the effects of monovalent ions on neutral model lipid membranes were characterized. Herein physical properties of physiologically relevant anionic membranes in the presence of monovalent cations and oxidized lipids were studied. Hydration and mobility of the lipid bilayer at glycerol level were investigated using fluorescent solvent relaxation technique. In the first part of this work the interactions of cations (Na+ , K+ , Cs+ ) with negatively charged POPC/POPS lipid mixture, which is a good model of inner leaflet of cellular membrane, were studied. The presence of cations resulted in dehydration and substantial hinderence of mobility of hydrated lipids at the glycerol level probed by Laurdan. Clear specificity of those effects, which correlated with Hofmeister series have been observed. In the second part of the work truncated oxidized phospholipids, oxPLs (PazePC, PoxnoPC, PGPC, POVPC), which are known to be important in pathophysiology of numerous diseases, were investigated. 10 mol% of each oxPL was incorporated into neutral and anionic lipid bilayers, the hydration and mobility of which were measured in water or in KCl solution. The results reveal complex interactions between oxPLs, negatively charged lipids, and K+ . In...
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