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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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Functionalized hybrid polymer structures for biomedical applications
Rabyk, Mariia ; Štěpánek, Petr (advisor) ; Sedláková, Zdeňka (referee) ; Kotek, Jan (referee)
This doctoral thesis is dedicated to the synthesis and characterization of novel functionalized hybrid structures for biomedical purposes. Systems reported in this work can be subdivided into the two main groups: natural-based materials and synthetic amphiphilic block copolymers. Both groups were studied as perspective theranostic agents for medical applications. In the first group, natural polysaccharides glycogen and mannan were selected as starting materials for preparation of novel nanoconjugates that possess ability for multimodal detection in vivo. Because grafting of natural macromolecules with synthetic polymers generally slows down the biodegradation rate, both polysaccharides were modified in two different ways to form nanoprobes with or without poly(2-methyl-2-oxazoline)s chains. The prepared nanoconjugates were functionalized with N-hydroxysuccinimide-activated fluorescence and magnetic resonance imaging labels. The resulting materials were tested both in vitro and in vivo and were shown to be completely biocompatible, biodegradable and exhibit some extra benefits in terms of their practical usage in biomedicine. Glycogen was functionalized with allyl and propargyl groups with following freeze-drying from aqueous solutions to form nano- and microfibrous materials. The presence of both...
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