Multifunctional polymers are interesting substances for the formulation of drug molecules that cannot be administered in their pure form due to their pharmacokinetic profiles or side effects. Polymer-drug formulations can enhance pharmacological properties or create tissue specificity by encapsulating the drug into nanocontainers, or stabilizing nanoparticles for drug transport. We present the synthesis of multifunctional poly(2-ethyl-2-oxazoline-co-2-glyco-2-oxazoline)s containing two reactive end groups, and an additional hydrophobic anchor at one end of the molecule. These polymers were successfully used to stabilize (solid) lipid nanoparticles ((S)LNP) consisting of tetradecan-1-ol and cholesterol with their hydrophobic anchor. While the pure polymers interacted with GLUT1-expressing cell lines mainly based on their physicochemical properties, especially via interactions of the hydrophobic anchor with membranous compartments of the cells, LNP-cell interactions hinted toward an influence of the glucosylation on particle-cell interactions. The presented LNP are therefore promising systems for the delivery of drugs into GLUT1-expressing cell lines.
- MeSH
- cholesterol chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- lidé MeSH
- lipidy chemie MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- oxazoly * chemie MeSH
- polymery chemie MeSH
- přenašeč glukosy typ 1 metabolismus MeSH
- systémy cílené aplikace léků metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cholesterol MeSH
- lipidy MeSH
- nosiče léků MeSH
- oxazoly * MeSH
- poly(2-oxazoline) MeSH Prohlížeč
- polymery MeSH
- přenašeč glukosy typ 1 MeSH
Poly(2-oxazoline) is a promising new class of polymeric materials due to their antibiofouling properties and good biocompatibility. Poly(2-oxazoline) coatings can be deposited on different substrates via plasma polymerization, which can be more advantageous than other coating methods. The aim of this study is to deposit poly(2-oxazoline) coatings using a surface dielectric barrier discharge burning in nitrogen at atmospheric pressure using 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline vapours as monomers and compare the film properties. For the comparison, the antibacterial and cytocompatibility tests were peformed according to ISO norms. The antibacterial tests showed that all the deposited films were highly active against Staphylococcus aureus and Escherichia coli bacteria. The chemical composition of the films was studied using FTIR and XPS, and the film surface's properties were studied using AFM and surface energy measurement. The cytocompatibility tests showed good cytocompatibility of all the deposited films. However, the films deposited from 2-methyl-2-oxazoline exhibit better cytocompatibility. This difference can be explained by the different chemical compositions and surface morphologies of the films deposited from different monomers.
- Klíčová slova
- antibiofouling, plasma polymer, poly(2-oxazoline),
- MeSH
- antibakteriální látky * farmakologie MeSH
- Escherichia coli MeSH
- oxazoly * farmakologie chemie MeSH
- polymerizace MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 2-ethyl-2-oxazoline MeSH Prohlížeč
- 2-methyl-2-oxazoline MeSH Prohlížeč
- antibakteriální látky * MeSH
- oxazoly * MeSH
Research on the subject of smart biomaterials has become a cornerstone of tissue engineering and regenerative medicine. Herein, the authors report on developing magnetic hydrogels that combine high biocompatibility and remarkable activity in magnetic fields. We fabricated magnetic hydrogels based on poly(2-ethyl-2-oxazoline) (POx) via living ring-opening cationic polymerization with in-situ embedding of the carbonyl iron (CI) particles. Investigation was made as to the effect exerted by the concentration of CI on magnetic, viscoelastic/magnetorheological properties, the degree of equilibrium swelling, and cytotoxicity. The hydrogels exhibited an open pore structure, as evidenced by computed tomography (CT) imaging. Susceptibility measurements revealed the concentration-dependent field-induced particle restructuration indicating elongation/contraction of the material, thereby determining the potential for magneto-mechanical stimulation of the cells. The POx-based magnetic hydrogels were amphiphilic in character, showing decrease in their capability to hold liquid alongside increase in CI concentration. Viscoelastic measurements suggested that interaction occurred between the particles and matrix based on inconsistency between the experimental storage modulus and the Krieger-Dougherty model. The synthesized materials exhibited excellent biocompatibility toward the 3T3 fibroblast cell line in tests of extract toxicity and direct contact cytotoxicity (ISO standards). The unique combination of properties exhibited by the material - magneto-mechanical activity and biocompatibility - could prove favorable in fields such as biomedicine and biomechanics.
- Klíčová slova
- Biomaterial, Biomedical application, Living cationic polymerization, Magnetic gel, Magnetorheology, Poly(2-oxazoline),
- MeSH
- buňky 3T3 MeSH
- fibroblasty účinky léků MeSH
- hydrogely chemická syntéza chemie farmakologie MeSH
- magnetické pole MeSH
- myši MeSH
- oxazoly chemická syntéza chemie farmakologie MeSH
- povrchové vlastnosti MeSH
- velikost částic MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- hydrogely MeSH
- oxazoly MeSH
- poly(2-oxazoline) MeSH Prohlížeč
Poly(2-alkyl-2-oxazoline)s (PAOx) represent a class of emerging polymers that can substitute or even outperform poly(ethylene oxide) (PEO) standard in various applications. Despite the great advances in PAOx research, there is still a gap in the direct experimental comparison of antifouling properties between PAOx and the golden standard PEO when exposed to blood. Motivated by this, we developed a straightforward protocol for the one-pot PAOx polymerization and surface coating by a "grafting to-" approach. First, we synthesized a library of hydrophilic poly(2-methyl-2-oxazoline)s (PMeOx) and poly(2-ethyl-2-oxazoline)s (PEtOx) with molar mass ranging from 1.5 to 10 kg/mol (DP = 16-115). The PAOx living chains were directly terminated by amine and hydroxyl groups of polydopamine (PDA) anchor layer providing the highest so far reported grafting densities ranging from 0.2 to 2.1 chains/nm2. In parallel, PEO chains providing the same degree of polymerization (molar mass from 1.2 to 5 kg/mol, DP = 28-116) bearing thiol groups were grafted to PDA. The thickness, surface-related parameters, covalent structure, and antifouling properties of the resulting polymer brushes were determined via various surface sensitive techniques. The comparison of the synthesized PAOx and PEO brushes led us to the conclusion that at the same surface-related parameters, PMeOx brushes show significantly better antifouling character when challenged against human blood plasma.
- MeSH
- hydrofobní a hydrofilní interakce účinky léků MeSH
- krevní plazma účinky léků MeSH
- lidé MeSH
- molekulová hmotnost MeSH
- oxazoly chemická syntéza chemie farmakologie MeSH
- polyaminy chemická syntéza chemie farmakologie MeSH
- polyethylenglykoly chemická syntéza chemie farmakologie MeSH
- polymerizace MeSH
- polymery chemická syntéza chemie farmakologie MeSH
- povrchové vlastnosti účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- oxazoly MeSH
- poly(2-oxazoline) MeSH Prohlížeč
- polyaminy MeSH
- polyethylenglykoly MeSH
- polymery MeSH
OBJECTIVE: 19F MRI requires biocompatible and non-toxic soluble contrast agents with high fluorine content and with suitable 19F relaxation times. Probes based on a DOTP chelate with 12 magnetically equivalent fluorine atoms (DOTP-tfe) and a lanthanide(III) ion shortening the relaxation times were prepared and tested. METHODS: Complexes of DOTP-tfe with trivalent paramagnetic Ce, Dy, Ho, Tm, and Yb ions were synthetized and characterized. 19F relaxation times were determined and compared to those of the La complex and of the empty ligand. In vitro and in vivo 19F MRI was performed at 4.7 T. RESULTS: 19F relaxation times strongly depended on the chelated lanthanide(III) ion. T1 ranged from 6.5 to 287 ms, T2 from 3.9 to 124.4 ms, and T2* from 1.1 to 3.1 ms. All complexes in combination with optimized sequences provided sufficient signal in vitro under conditions mimicking experiments in vivo (concentrations 1.25 mM, 15-min scanning time). As a proof of concept, two contrast agents were injected into the rat muscle; 19F MRI in vivo confirmed the in vivo applicability of the probe. CONCLUSION: DOTP-based 19F probes showed suitable properties for in vitro and in vivo visualization and biological applications. The lanthanide(III) ions enabled us to shorten the relaxation times and to trim the probes according to the actual needs. Similar to the clinically approved Gd3+ chelates, this customized probe design ensures consistent biochemical properties and similar safety profiles.
- Klíčová slova
- Fluorine-19 magnetic resonance imaging, Lanthanide series elements, Macrocyclic ligand complexes, Molecular probes, Phosphinic acid complexes, Relaxation times,
- MeSH
- chelátory chemie MeSH
- fluor chemie MeSH
- ionty MeSH
- kontrastní látky chemie MeSH
- krysa rodu Rattus MeSH
- lanthanoidy chemie MeSH
- ligandy MeSH
- magnetismus MeSH
- molekulová hmotnost MeSH
- oxazoly chemie MeSH
- pyrimidinony chemie MeSH
- zobrazování fluorovou magnetickou rezonancí * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 2,3-dihydro-5H-oxazolo(3,2-a)thieno(3,2-d)pyrimidin-5-one MeSH Prohlížeč
- chelátory MeSH
- fluor MeSH
- ionty MeSH
- kontrastní látky MeSH
- lanthanoidy MeSH
- ligandy MeSH
- oxazoly MeSH
- pyrimidinony MeSH
Herein, we describe a new method for the synthesis of superhydrophilic poly(2-alkyl-2-oxazoline)s (PAOx) from poly(2-ethyl-2-oxazoline) (PEtOx). A well-defined linear polyethylenimine was prepared from PEtOx by controlled acidic hydrolysis of its side-chains followed by reacylation with different carboxylic acids. Using this protocol, we obtained a series of new hydrophilic PAOx containing side-chain ether groups with potential in biomaterials science. The relative hydrophilicity of the polymers was assessed, revealing that poly(2-methoxymethyl-2-oxazoline) (PMeOMeOx) is the most hydrophilic PAOx reported to date. Additionally, the amorphous poly(2-methoxy-ethoxy-ethoxymethyl-2-oxazoline) (PDEGOx) shows the lowest reported glass transition temperature (-25 °C) within the PAOx family to date. The biomedical potential of the prepared polymers was further fortified by an in vitro cytotoxicity study, where all polymers appeared to be noncytotoxic. The described synthetic protocol is universal and can be extremely versatile, especially for PAOx that are difficult to prepare by conventional cationic ring-opening polymerization due to the monomer interference and/or degradation.
- MeSH
- HeLa buňky MeSH
- hydrofobní a hydrofilní interakce MeSH
- lidé MeSH
- oxazoly chemie MeSH
- polyethylenimin chemie MeSH
- tranzitní teplota MeSH
- vitrifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- oxazoly MeSH
- poly(2-oxazoline) MeSH Prohlížeč
- polyethylenimin MeSH
Among external stimuli used to trigger release of a drug from a polymeric carrier, ultrasound has gained increasing attention due to its non-invasive nature, safety and low cost. Despite this attention, there is only limited knowledge about how materials available for the preparation of drug carriers respond to ultrasound. This study investigates the effect of ultrasound on the release of a hydrophobic drug, dexamethasone, from poly(2-oxazoline)-based micelles. Spontaneous and ultrasound-mediated release of dexamethasone from five types of micelles made of poly(2-oxazoline) block copolymers, composed of hydrophilic poly(2-methyl-2-oxazoline) and hydrophobic poly(2-n-propyl-2-oxazoline) or poly(2-butyl-2-oxazoline-co-2-(3-butenyl)-2-oxazoline), was studied. The release profiles were fitted by zero-order and Ritger-Peppas models. The ultrasound increased the amount of released dexamethasone by 6% to 105% depending on the type of copolymer, the amount of loaded dexamethasone, and the stimulation time point. This study investigates for the first time the interaction between different poly(2-oxazoline)-based micelle formulations and ultrasound waves, quantifying the efficacy of such stimulation in modulating dexamethasone release from these nanocarriers.
- MeSH
- dexamethason farmakokinetika MeSH
- dynamický rozptyl světla MeSH
- hydrofobní a hydrofilní interakce MeSH
- micely MeSH
- nosiče léků chemie farmakokinetika MeSH
- oxazoly chemie MeSH
- polymery chemie MeSH
- systémy cílené aplikace léků metody MeSH
- transmisní elektronová mikroskopie MeSH
- ultrazvuk metody MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dexamethason MeSH
- micely MeSH
- nosiče léků MeSH
- oxazoly MeSH
- poly(2-oxazoline) MeSH Prohlížeč
- polymery MeSH
A conceptually new bimodal immunoradiotherapy treatment was demonstrated using thermoresponsive polymer β-glucan-graft-poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline) bearing complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with yttrium-90(III) at the graft ends. The behavior of this thermoresponsive polymer in aqueous solutions was studied, and it showed the appropriate cloud point temperature for brachytherapy applications. The polymer was tested in vitro, and it exhibited nontoxicity and active uptake into cancer cells and macrophages with colocalization in the lysosomes and macrophagosomes. Moreover, the observed oxidative burst response of the leukocytes established the immunostimulatory properties of the polymer, which were also studied in vivo after injection into the thigh muscles of healthy mice. The subsequent histological evaluation revealed the extensive immune activation reactions at the site of injection. Furthermore, the production of tumor necrosis factor α induced by the prepared polymer was observed in vitro, denoting the optimistic prognosis of the treatment. The biodistribution study in vivo indicated the formation of the polymer depot, which was gradually degraded and excluded from the body. The radiolabeled polymer was used during in vivo antitumor efficiency experiments on mice with EL4 lymphoma. The immunoradiotherapy group (treated with the radiolabeled polymer) demonstrated the complete inhibition of tumor growth during the beginning of the treatment. Moreover, 7 of the 15 mice were completely cured in this group, while the others exhibited significantly prolonged survival time compared to the control group. The in vivo experiments indicated the considerable synergistic effect of using immunoradiotherapy compared to separately using immunotherapy or radiotherapy.
- Klíčová slova
- Immunotherapy, Multimodal cancer therapy, Polyoxazoline, Radiotherapy, β-glucan,
- MeSH
- antibakteriální látky chemická syntéza farmakologie MeSH
- antitumorózní látky chemická syntéza farmakologie terapeutické užití MeSH
- aza sloučeniny chemie MeSH
- beta-glukany chemie MeSH
- brachyterapie metody MeSH
- heterocyklické sloučeniny monocyklické chemie MeSH
- imunitní systém účinky léků MeSH
- komplexní sloučeniny chemie MeSH
- leukocyty účinky léků metabolismus MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- nádorové buněčné linie MeSH
- oxazoly chemie MeSH
- oxidace-redukce MeSH
- polymery chemie MeSH
- radioimunoterapie metody MeSH
- radioizotopy ytria chemie MeSH
- Staphylococcus aureus účinky léků MeSH
- teplota MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid MeSH Prohlížeč
- antibakteriální látky MeSH
- antitumorózní látky MeSH
- aza sloučeniny MeSH
- beta-glukany MeSH
- heterocyklické sloučeniny monocyklické MeSH
- komplexní sloučeniny MeSH
- oxazoly MeSH
- polymery MeSH
- radioizotopy ytria MeSH
- Yttrium-90 MeSH Prohlížeč
Previous research has identified ribose aminooxazoline as a potential intermediate in the prebiotic synthesis of the pyrimidine nucleotides with remarkable properties. It crystallizes spontaneously from reaction mixtures, with an enhanced enantiomeric excess if initially enantioenriched, which suggests that reservoirs of this compound might have accumulated on the early Earth in an optically pure form. Ribose aminooxazoline can be converted efficiently into α-ribocytidine by way of 2,2'-anhydroribocytidine, although anomerization to β-ribocytidine by ultraviolet irradiation is extremely inefficient. Our previous work demonstrated the synthesis of pyrimidine β-ribonucleotides, but at the cost of ignoring ribose aminooxazoline, using arabinose aminooxazoline instead. Here we describe a long-sought route through ribose aminooxazoline to the pyrimidine β-ribonucleosides and their phosphate derivatives that involves an extraordinarily efficient photoanomerization of α-2-thioribocytidine. In addition to the canonical nucleosides, our synthesis accesses β-2-thioribouridine, a modified nucleoside found in transfer RNA that enables both faster and more-accurate nucleic acid template-copying chemistry.
- MeSH
- evoluce chemická * MeSH
- fosfáty chemická syntéza chemie MeSH
- fotochemické procesy * MeSH
- molekulární konformace MeSH
- oxazoly chemie MeSH
- pyrimidiny chemická syntéza chemie MeSH
- ribonukleosidy chemická syntéza chemie MeSH
- ribosa chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fosfáty MeSH
- oxazoly MeSH
- pyrimidine MeSH Prohlížeč
- pyrimidiny MeSH
- ribonukleosidy MeSH
- ribosa MeSH
Poly(2-alkenyl-2-oxazoline)s are promising functional polymers for a variety of biomedical applications, such as drug delivery systems, peptide conjugates, or gene delivery. In this study, poly(2-isopropenyl-2-oxazoline) (PIPOx) is prepared through free-radical polymerization initiated with azobisisobutyronitrile. Reactive 2-oxazoline units in the side chain support an addition reaction with different compounds containing a carboxylic group, which facilitates the preparation of polymers labeled with two different fluorescent dyes. The cytotoxicities of 2-oxazoline monomers, PIPOx, and fluorescently labeled PIPOx are evaluated in vitro using an 3-(4,5-Dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and ex vivo using a cell proliferation assay with adenosine triphosphate bioluminescence. The cell uptake of labeled PIPOx is used to determine the colocalization of PIPOx with cell organelles that are part of the endocytic pathway. For the first time, it is shown that poly(2-isopropenyl-2-oxazoline) is a biocompatible material and is suitable for biomedical applications; further, its immunomodulative properties are evaluated.
- Klíčová slova
- biocompatibility, cell proliferation, fluorescence, functionalization of polymers, poly(2-isopropenyl-2-oxazoline), splenocytes,
- MeSH
- biokompatibilní materiály chemická syntéza chemie farmakologie MeSH
- buněčná smrt účinky léků MeSH
- buňky 3T3 MeSH
- endocytóza účinky léků MeSH
- fibroblasty cytologie MeSH
- fluorescenční spektrometrie MeSH
- imunomodulace účinky léků MeSH
- konfokální mikroskopie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- organely účinky léků metabolismus MeSH
- oxazoly chemická syntéza chemie farmakologie MeSH
- polymery chemická syntéza chemie farmakologie MeSH
- polypropyleny chemická syntéza chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- slezina cytologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biokompatibilní materiály MeSH
- oxazoly MeSH
- poly(2-isopropenyl-2-oxazoline) MeSH Prohlížeč
- polymery MeSH
- polypropyleny MeSH
