Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase-separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer-supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two-phase kinetics (depot maturation, slow redissolution) with half-lives 2 weeks to 5 months, as depot vitrification prolonged their half-lives. Additionally, the decrease of TCP of a polymer solution increased the density of the intramuscular depot. Moreover, they detected secondary polymer depots in the kidneys and liver; these secondary depots also followed two-phase kinetics (depot maturation and slow dissolution), with half-lives 8 to 38 days (kidneys) and 15 to 22 days (liver). Overall, these findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications. Their methods may become a benchmark for future studies of polymer biodistribution.

• Keywords
• LCST, biodistribution, poly(2,2-difluoroethyl)acrylamide, poly(N,N-diethylacrylamide), poly(N-acryloylpyrolidine), poly(N-isopropylacrylamide), polyacrylamide, rational polymer design,
• MeSH
• Mice MeSH
• Polymers * MeSH
• Temperature MeSH
• Tissue Distribution MeSH
• Drug Liberation MeSH
• Water * MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Polymers * MeSH
• Water * MeSH

In situ 1H NMR characterization of copolymerization reactions of various 2-oxazoline monomers at different molar ratios offers detailed insight into the build-up and composition of the polymer chains. Various 2-oxazolines were copolymerized in one single solvent, butyronitrile, with 2-dec-9'-enyl-2-oxazoline, where the double bond allows for post-polymerization modification and can function as a crosslinking unit to form polymer networks. The types of the monomers and their molar ratios in the feed have a strong effect on the microstructure of the forming copolymer chains. Copolymers comprising 2-dec-9'-enyl-2-oxazoline and either 2-ethyl-, 2-isopropyl-, 2-butyl-, 2-heptyl, 2-nonyl- or 2-phenyl-2-oxazoline, show significant differences in sequential structure of copolymers ranging from block to gradient and random ordering of the monomer units. 1H NMR was found to be a powerful tool to uncover detailed oxazoline copolymerization kinetics and evolution of chain composition.

• Publication type
• Journal Article MeSH

Over the last few years, the development and relevance of 19F magnetic resonance imaging (MRI) for use in clinical practice has emerged. MRI using fluorinated probes enables the achievement of a specific signal with high contrast in MRI images. However, to ensure sufficient sensitivity of 19F MRI, fluorine probes with a high content of chemically equivalent fluorine atoms are required. The majority of 19F MRI agents are perfluorocarbon emulsions, which have a broad range of applications in molecular imaging, although the content of fluorine atoms in these molecules is limited. In this review, we focus mainly on polymer probes that allow higher fluorine content and represent versatile platforms with properties tailorable to a plethora of biomedical in vivo applications. We discuss the chemical development, up to the first imaging applications, of these promising fluorine probes, including injectable polymers that form depots that are intended for possible use in cancer therapy.

• Keywords
• 19F MRI probe, Fluorine, Magnetic resonance imaging (MRI), Molecular imaging, Polymer,
• MeSH
• Fluorine chemistry   MeSH
• Fluorocarbons chemistry   MeSH
• Hydrogen-Ion Concentration MeSH
• Contrast Media chemistry   MeSH
• Humans MeSH
• Molecular Probes chemistry   MeSH
• Molecular Imaging instrumentation   methods   MeSH
• Mice MeSH
• Polymers chemistry   MeSH
• Scattering, Radiation MeSH
• Reactive Oxygen Species metabolism   MeSH
• Light MeSH
• Temperature MeSH
• Fluorine-19 Magnetic Resonance Imaging methods   trends   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Fluorine MeSH
• Fluorocarbons MeSH
• Contrast Media MeSH
• Molecular Probes MeSH
• Polymers MeSH
• Reactive Oxygen Species MeSH