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Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polyacrylamides
Groborz, Ondřej
6 Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polyacrylamides Author: Ondřej Groborz Supervisor: doc. Mgr. Martin Hrubý, Ph.D., DSc. Institute of Macromolecular Chemistry, Czech Academy of Sciences Advisers: Ing. Pavel Švec RNDr. Lenka Loukotová, PhD. Abstract Polymer solutions with lower critical solution temperature (LCST) undergo a phase separation when heated above their cloud point temperature (TCP). These thermoresponsive polymers have numerous promising medicinal applications, such as in situ depot-forming radiotherapy (brachytherapy), controlled drug-release, immuno-radiotherapy, injectable thermogelling for tissue engineering and cell culture and magnetic resonance imaging (MRI), among others. Yet, despite extensive research on medicinal applications of thermoresponsive polymers, their fate after their administration remains largely unknown. Thus, in our study, we synthesized and thoroughly characterized four different thermoresponsive polyacrylamides, namely poly(N-(2,2-difluoroethyl)acrylamide), poly(N- isopropylacrylamide), poly(N,N-diethylacrylamide) and poly(N-acryloylpyrrolidine) under physiologically relevant conditions. Subsequently, we determined their biodistribution kinetics in mice and proposed a data-based pharmacological model to describe their in vivo behaviour,...
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Biomedical applications of cationic gold nanoparticles
Žárská, Monika ; Hodný, Zdeněk (advisor) ; Králová, Jarmila (referee) ; Bačáková, Lucie (referee)
Cationic gold nanoparticles (GNPs) represent innovative materials promising for treating severe diseases, including cancer. Due to the unique physical properties of colloidal gold, GNPs have been shown to function as theranostics agents, allowing the diagnosis and treatment of the pathological area simulataneously. In addition, a cationic surface charge of GNPs provides extensive nanoparticle-cell interactions. However, despite the great potential in clinical medicine, various types of GNPs have contradictory results, and the studies dealing with the biological and therapeutic properties of cationic GNPs are inconsistent. This doctoral thesis summarizes the current state of knowledge about the biological properties and medical applications of GNPs focusing specifically on positively charged GNPs. A overview of plasmonic photothermal therapy (PPTT) as a cancer treatment strategy is included. Using a step-by-step research approach, our results then characterize the therapeutic potential of GNPs with a specific shape of nanorods (GNRs) and surface modification with quaternary ammonium salt (QAS). At first, the elementary factors participating in the interaction of cationic GNRs with cells, their transmembrane and intracellular transport, and long-term persistence in cells were described. Subsequently,...
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Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polyacrylamides
Groborz, Ondřej ; Hrubý, Martin (advisor) ; Matějíček, Pavel (referee)
6 Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polyacrylamides Author: Ondřej Groborz Supervisor: doc. Mgr. Martin Hrubý, Ph.D., DSc. Institute of Macromolecular Chemistry, Czech Academy of Sciences Advisers: Ing. Pavel Švec RNDr. Lenka Loukotová, PhD. Abstract Polymer solutions with lower critical solution temperature (LCST) undergo a phase separation when heated above their cloud point temperature (TCP). These thermoresponsive polymers have numerous promising medicinal applications, such as in situ depot-forming radiotherapy (brachytherapy), controlled drug-release, immuno-radiotherapy, injectable thermogelling for tissue engineering and cell culture and magnetic resonance imaging (MRI), among others. Yet, despite extensive research on medicinal applications of thermoresponsive polymers, their fate after their administration remains largely unknown. Thus, in our study, we synthesized and thoroughly characterized four different thermoresponsive polyacrylamides, namely poly(N-(2,2-difluoroethyl)acrylamide), poly(N- isopropylacrylamide), poly(N,N-diethylacrylamide) and poly(N-acryloylpyrrolidine) under physiologically relevant conditions. Subsequently, we determined their biodistribution kinetics in mice and proposed a data-based pharmacological model to describe their in vivo behaviour,...
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