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Browsing by Subject "farmakokineettinen malli"

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  • Nurmi, Riikka (2017)
    Liposomes are spherical nano-sized drug delivery systems which are composed of lipid bilayer. With liposomes drugs can be targeted for example to tumours and targeting can be passive or active. Drug release from liposomes can also be activated by different methods. Light is very promising triggering method, because it enables drug release at specific time and site. This study examined light activated indocyanine green (ICG) liposomes. Drug release from liposomes happens because ICG converts light energy to heat. ICG is clinically approved imaging agent, so ICG liposomes are very promising drug delivery systems even for clinical use. Liposomes were prepared by thin-film hydration method. One aim of the study was to prepare as small ICG-liposomes as possible. The bigger 100 nm liposomes were studied in three different formulations and the purpose was to find differences between those formulations. In formulation A ICG was in PEGs, in formulation B ICG was in lipid bilayer with no PEGs and in formulation C ICG was supposed to be in lipid bilayer although the formulation C included PEGs. In this study, the cell up take of ICG liposomes was studied with pharmacokinetic model and data from in vitro studies was supposed to use in a pharmacokinetic model. In this study, it was possible to prepare 40 nm sized ICG-liposomes. Small liposomes did not release encapsulated calsein as well as bigger 100 nm liposomes. The decreased release from smaller liposomes was probably explained by the results witch pointed out that transition temperature of small liposomes was higher than transition temperature of bigger liposomes. In the future, the lipid composition of the small liposomes need to be reoptimized, that the release would be more effective. This study however proved that small ICG-liposomes can be prepared and the small size lasts even over three months. Three different formulations of 100 nm liposomes were studied and the differences between the properties of the formulations were found. ICG in the lipid bilayer changed properties of the formulation B and the passive release of the calsein and release during the lightning were increased. In formulation C transition temperature was decreased and its storage life was lower than in other formulations. Formulation A was best for the next studies and the phospholipid composition of other formulations need to be optimated that drug release and storage life would be good enough. Intracellular release properties of liposomes were studied with Sytox red probe. Fluorescence of Sytox red increases when it binds with DNA or RNA. With this study, it was proved that liposomes release Sytox red inside the cells and that the lightning time affects to the release. The results weren't useable for pharmacokinetic model, so the model was made based by literature. Pharmacokinetic model can be used in the future studies and different in vitro or in vivo results can be combined with the model.
  • Juuti, Hanne (2010)
    The blood-brain barrier protects brain from xenobiotics that are in blood. Different in vivo and in vitro methods have been developed for studying blood brain barrier and those can be found in the literature. There are only few computational models pharmacokinetics of compounds in the brain. In this study permeability factors, which were measured in vitro or in vivo, were collected from literature. Additionally two different pharmacokinetic computer models of blood-brain barrier were described. One of which is called microdialysis model and the other efflux model. Microdialysis model is a very simple two compartmental model, the compartments being the blood and the brain. Five substances were simulated according to the values measured in vivo in rat. The model did not correlate well with the in vivo results, because of the simplicity of the model as the model missed the compartment of brain tissue and the kinetics of transporters. Efflux model has three compartments, blood, blood brain barrier endothelial cells and brain. The model was used to study the impact of the of efflux transporter at the luminal barrier of endothelial cells and passive permeability to the steady-state concentration of a compound in the brain extracellular fluid with theoretical simulations. The relation between free drug concentrations in blood and brain extracellular fluid (Kp,uu) was studied. The impact of Michaelis-Menten kinetics of efflux transporter to the concentration of compound was shown in the results. The efflux model is suitable for theoretical simulations. It is possible to add new active transporters. With theoretical simulations the results from in vitro and in vivo studies can be combined and the different factors can be studied in one simulation.