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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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Development of liquisolid systems for colon targeting
Ogadah, Chiazor Ugo ; Vraníková, Barbora (advisor) ; Zámostný, Petr (referee) ; Gajdziok, Jan (referee)
Univerzita Karlova, Farmaceutická Fakulta V Hradci Králové Školicí pracoviště: Katedra Farmaceutické Technologie Doktorský studijní program: Farmaceutická Technologie Kandidátka: Mgr. Chiazor Ugo Ogadah Školitelka: doc. PharmDr. Barbora Vraníková, Ph.D. Konzultantka: doc. Prof. PharmDr. Zdeňka Šklubalová, Ph.D. Název dizertační práce: Vývoj liquisolid systémů s cíleným přívodem léčiva do kolonu V lokální nebo systémové terapii chorob tlustého střeva mají systémy cílící do kolonu slibnou perspektivu. Úspěch však představuje výzvu díky fyziologickým bariérám trávicího traktu. Pokud zvýšení rozpustnosti léčiva předchází cílení, lze rozpouštění, jako krok limitující rychlost, obejít, urychlit vstřebání léčiva a zvýšit jeho perorální biodostupnost. Pro optimalizaci dávky a terapeutického efektu je kromě toho potřebné zadržet přípravek v místě cílení. Cílem této práce je proto vývoj systému pro doručení a cílení omezeně rozpustného léčiva cyklosporinu A (CyA) do kolonu. V první části experimentu byly využity preformulační studie k dosažení zvýšené rozpustnosti a zrychleného uvolnění CyA pomocí tzv. liquisolid sytému (LSS) nebo přípravou interaktivních směsí společným mletím (komletím). To zahrnovalo výběr vhodného nosiče a hodnocení jeho vlastností při mletí, stejně jako výběr netěkavého...
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Magnetic carriers and their practical use
Chlopková, Barbora ; Rittich, Bohuslav (referee) ; Španová, Alena (advisor)
The theoretical part summarizes the current knowledge for practical use of magnetic carriers in molecular diagnostics. It includes both already used methods and methods with potential for the future. In the experimental part was tested by use of magnetic media for isolation of DNA from a dairy product and a bacterial culture. It was confirmed that the magnetic carrier DNA was isolated in quantity and quality suitable for carrying out polymerase chain reaction.
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Synthesis of self-immolative linkers suitable for bioconjugation
Taraj, Lukáš ; Baszczyňski, Ondřej (advisor) ; Jindřich, Jindřich (referee)
Self-immolative (SI) linkers are chemical constructs that undergo controlled self- fragmentation based on an appropriate stimulus, e.g., activation by light or a chemical agent. SI linkers are used in the targeted delivery of drugs, in the construction of probes for biochemistry, or in various polymers. The aim of the thesis will be the synthesis of new phosphorus-based SI linkers, which will contain a reactive chemical function for conjugation with thiols. Such a function will be, for example, a vinyl phosphonate or alkynyl phosphonate group. The aim of the work will be to examine the synthesis, self-immolation, stability, and the possibility of conjugability of such linkers with thiols, e.g., cysteine, glutathione, etc. The content of the student's work will be the synthesis of SI linkers, analysis of the obtained data, planning and monitoring of chemical experiments, and writing the diploma thesis. Keywords: self-immolative, bioconjugation, phosphorus, drug delivery
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Biocompatible polymer systems for medical application
Hrochová, Michaela ; Etrych, Tomáš (advisor) ; Bárta, František (referee)
Polymer carriers for drug delivery are still an extensively studied topic in many research laboratories around the world. Polymer systems have an important role in the case of oncological diseases, where they allow to increase the therapeutic effect and significantly reduce the side effects of treatment. The present thesis is primarily focused on the synthesis of novel water-soluble biodegradable polymer systems based on N-(2- hydroxypropyl)methacrylamide enabling the treatment of solid tumors. As part of the work, four bifunctional transfer agents have been developed, which enable the direct synthesis of symmetric diblock polymers with a size of 20,000-100,000 g∙mol-1 with RAFT polymerization. The transfer agents introduce hydrolytically labile ester bonds into the structure of diblock polymers, which allow the diblock to break down into smaller fragments that can be excreted by the kidneys. The different structures of the chain transfer agents make it possible to control the breakdown of diblocks over a wide time range from 2,5 hours to 21 days. The advantages of the prepared diblock carriers are primarily the one-step synthesis, adjustable degradation time, and the possibility of modifying the end groups of the polymer chain. In the presence of bifunctional transfer agents, copolymers of HPMA...
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Stimuli - responsive nanoparticles with boronic ester linkages as a potential carrier for drug delivery
Hlavatovičová, Eva
This thesis deals with the post-polymerization functionalization of a pH-responsive poly(styrene)-b-poly(4-vinyl pyridine)-b-poly(ethylene oxide) triblock terpolymer with stimuli responsive and diol-binding 2-bromomethyl-4-fluorophenylboronic acid and 2- bromomethyl-phenylboronic acid suitable for biomedical applications. A reproducible method of quaternization of poly(4-vinyl pyridine) block with prescriptible quaternization ratio was developed and the reaction yield was analyzed by 11 B, 1 H NMR and infrared spectroscopy. A reproducible self-assembly protocol for stable nanoparticles from functionalized stimuli-responsive triblock terpolymer was found, and the nanoparticles were studied by static, dynamic and electrophoretic light scattering, and cryogenic transmission electron microscopy. Fluorescence and UV-VIS spectroscopy measurements were performed for description of boron-ester linkages formation and hydrolysis with model drug Alizarin as a study of encapsulation and release reactions together with sugar sensing reactions for potential drug delivery.
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Biological characteristics of polysccharide based contrast agents for cancer diagnostics
Křivánková, Markéta
Despite all the progress made in the treatment of cancer in recent years, it is still necessary to continue with the research of more effective and specific drugs. In recent years, there has been a growing interest in personalized medicine and its application through drug delivery systems, which could help increase the specificity of cancer treatment and subsequently its effectiveness. Drug delivery systems can use different platforms for their design, whether they are liposomes, micelles, nano crystals or others. A very interesting platform for the construction of drug delivery systems are polysaccharides, which were, as carriers of contrast agents in order to effectively display tumours, characterized in this doctoral thesis. But polysaccharides are interesting for more reasons. Both by its availability, and by its biocompatibility and non-toxic character. In this doctoral thesis we deal with two types of polysaccharides conjugates with linked contrast agents for magnetic resonance and fluorescent imaging. The first type of polysaccharide is glycogen, the second is mannan. Both constructs - glycogen and mannan based, were synthesized in a version with and without polymethyloxazolin, which should prolong their circulation in the organism. Both types of polysaccharide conjugates used passive...
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Biological characteristics of polysccharide based contrast agents for cancer diagnostics
Křivánková, Markéta ; Jirák, Daniel (advisor) ; Shapoval, Oleksandr (referee) ; Vannucci, Luca Ernesto (referee)
Despite all the progress made in the treatment of cancer in recent years, it is still necessary to continue with the research of more effective and specific drugs. In recent years, there has been a growing interest in personalized medicine and its application through drug delivery systems, which could help increase the specificity of cancer treatment and subsequently its effectiveness. Drug delivery systems can use different platforms for their design, whether they are liposomes, micelles, nano crystals or others. A very interesting platform for the construction of drug delivery systems are polysaccharides, which were, as carriers of contrast agents in order to effectively display tumours, characterized in this doctoral thesis. But polysaccharides are interesting for more reasons. Both by its availability, and by its biocompatibility and non-toxic character. In this doctoral thesis we deal with two types of polysaccharides conjugates with linked contrast agents for magnetic resonance and fluorescent imaging. The first type of polysaccharide is glycogen, the second is mannan. Both constructs - glycogen and mannan based, were synthesized in a version with and without polymethyloxazolin, which should prolong their circulation in the organism. Both types of polysaccharide conjugates used passive...
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