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Synthesis of triblock terpolymers as a tool for preparation of smart drug delivery nanosystems
Orságh, Martin ; Uchman, Mariusz Marcin (advisor) ; Fernandez Alvarez, Roberto (referee)
In this thesis, we describe the synthesis and self-assembly of new photo-responsive triblock terpolymers by RAFT polymerization. These triblock terpolymers were characterized by GPC, NMR and IR spectroscopy. The resulting nanoparticles were characterized by DLS, SAXS and Cryo-EM. To avoid problems with RAFT polymerization of the photo-responsive monomer o- nitrobenzyl acrylate, we used naphthacyl methacrylate, a new RAFT-polymerizable photo- responsive monomer. In addition, we used phenylboronic acid moieties to conjugate model drugs with our triblock terpolymers via dynamic covalent bonding and studied stimuli-triggered release of a model drug-like compound, Alizarin Red S. Our results showed that naphthacyl methacrylate is indeed polymerizable by RAFT and that such polymers retain photo-responsive properties. We were also able to bind Alizarin Red S to the polymer via boronate ester linkage and trigger its release by dopamine or fructose addition, both of which are biologically relevant compounds. Therefore, our photo- and diol-responsive nanoparticles open up opportunities for developing new drug-delivery systems.
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Design of boron cluster-containing nanostructuresin solution
Fernandez Alvarez, Roberto ; Matějíček, Pavel (advisor) ; Machalová Šišková, Karolína (referee) ; Cígler, Petr (referee)
Thesis The main objective of this thesis is the study of boron cluster compounds in solution, their interaction with polymers and the formation of nanostructures. Most of the work was focused around cobalt bis(dicarbollide) (COSAN) but the incorporation of carborane into polymers was also studied. The idea was to close the knowledge gap around the way COSAN aggregates and continue the line of the laboratory in leading this topic. Therefore, we performed in-depth analysis of isothermal titration calorimetry curves to determine the aggregation number at concentrations around the critical micellar concentration (CMC). Thus, the aggregation number obtained was an improvement over previous data obtained a much higher concentration. The use of acetonitrile as a cosolvent in the micellization process helped formulate a model describing how C-H bonds in the COSAN micelles are directed towards the inside of the micelle. Furthermore, COSAN was used as a model drug for loading nanocarriers composed of hydrophobic core and charged corona. The importance of this work relies on the creation of guidelines for drug loading into similar polymeric vectors in order to determine how the nanocarrier will be affected. With the help of coarse-grained simulations, we determined that changes in the hydrophobicity of the...
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