poly(2,2-difluoroethyl)acrylamide Dotaz Zobrazit nápovědu
Fluorine-19 MRI is a promising noninvasive diagnostic method. However, the absence of a nontoxic fluorine-19 MRI tracer that does not suffer from poor biodistribution as a result of its strong fluorophilicity is a constant hurdle in the widespread applicability of this otherwise versatile diagnostic technique. The poly[N-(2-hydroxypropyl)methacrylamide]-block-poly[N-(2,2-difluoroethyl)acrylamide] thermoresponsive copolymer was proposed as an alternative fluorine-19 MRI tracer capable of overcoming such shortcomings. In this paper, the internal structure of self-assembled particles of this copolymer was investigated by various methods including 1D and 2D NMR, dynamic light scattering (DLS), small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS). The elucidated structure appears to be that of a nanogel with greatly swollen hydrophilic chains and tightly packed thermoresponsive chains forming a network within the nanogel particles, which become more hydrophobic with increasing temperature. Its capacity to provide a measurable fluorine-19 NMR signal in its aggregated state at human body temperature was also investigated and confirmed. This capacity stems from the different fluorine-19 nuclei relaxation properties compared to those of hydrogen-1 nuclei.
- Klíčová slova
- PDFEA, PHPMA, diblock copolymer, fluorine-19, magnetic resonance imaging, self-assembly,
- Publikační typ
- časopisecké články MeSH
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.
- Klíčová slova
- LCST, biodistribution, poly(2,2-difluoroethyl)acrylamide, poly(N,N-diethylacrylamide), poly(N-acryloylpyrolidine), poly(N-isopropylacrylamide), polyacrylamide, rational polymer design,
- MeSH
- myši MeSH
- polymery * MeSH
- teplota MeSH
- tkáňová distribuce MeSH
- uvolňování léčiv MeSH
- voda * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- polymery * MeSH
- voda * MeSH
Gelatin-based photo-crosslinkable hydrogels are promising scaffold materials to serve regenerative medicine. They are widely applicable in additive manufacturing, which allows for the production of various scaffold microarchitectures in line with the anatomical requirements of the organ to be replaced or tissue defect to be treated. Upon their in vivo utilization, the main bottleneck is to monitor cell colonization along with their degradation (rate). In order to enable non-invasive visualization, labeling with MRI-active components like N-(2,2-difluoroethyl)acrylamide (DFEA) provides a promising approach. Herein, we report on the development of a gelatin-methacryloyl-aminoethyl-methacrylate-based biomaterial ink in combination with DFEA, applicable in digital light processing-based additive manufacturing towards bone tissue regeneration. The fabricated hydrogel constructs show excellent shape fidelity in line with the printing resolution, as DFEA acts as a small molecular crosslinker in the system. The constructs exhibit high stiffness (E = 36.9 ± 4.1 kPa, evaluated via oscillatory rheology), suitable to serve bone regeneration and excellent MRI visualization capacity. Moreover, in combination with adipose tissue-derived stem cells (ASCs), the 3D-printed constructs show biocompatibility, and upon 4 weeks of culture, the ASCs express the osteogenic differentiation marker Ca2+.
Thermoresponsive polymers showing cloud point temperatures (CPT) in aqueous solutions are very promising for the construction of various systems in biomedical field. In many of these applications these polymers get in contact with ionizing radiation, e.g., if they are used as carriers for radiopharmaceuticals or during radiation sterilization. Despite this fact, radiosensitivity of these polymers is largely overlooked to date. In this work, we describe the effect of electron beam ionizing radiation on the physicochemical and phase separation properties of selected thermoresponsive polymers with CPT between room and body temperature. Stability of the polymers to radiation (doses 0-20 kGy) in aqueous solutions increased in the order poly(N-vinylcaprolactam) (PVCL, the least stable) ≪ poly[N-(2,2-difluoroethyl)acrylamide] (DFP) < poly(N-isopropylacrylamide) (PNIPAM) ≪ poly(2-isopropyl-2-oxazoline-co-2-n-butyl-2-oxazoline) (POX). Even low doses of β radiation (1 kGy), which are highly relevant to the storage of polymer radiotherapeutics and sterilization of biomedical systems, cause significant increase in molecular weight due to cross-linking (except for POX, where this effect is weak). In the case of PVCL irradiated with low doses, the increase in molecular weight induced an increase in the CPT of the polymer. For PNIPAM and DFP, there is strong chain hydrophilization leading to an increase in CPT. From this perspective, POX is the most suitable polymer for the construction of delivery systems that experience exposure to radiation, while PVCL is the least suitable and PNIPAM and DFP are suitable only for low radiation demands.
- MeSH
- akrylové pryskyřice MeSH
- molekulová hmotnost MeSH
- nukleární lékařství * MeSH
- polymery analýza MeSH
- teplota MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- akrylové pryskyřice MeSH
- polymery MeSH
