Structure elucidation and toxicological evaluation of cyclic Polyethersulfone oligomers present in extracts of membrane filters. - In: Polymer engineering & science, ISSN 1548-2634, Bd. 62 (2022), 9, S. 2817-2825
Polyethersulfone (PES) is a widely used polymer in consumer and technical products. An important application is PES membranes used in the biopharmaceutical industry for sterilizing-grade filtration and for filtration of food and beverages. For both uses, detailed information about migrating compounds that can be extracted from the polymeric material into a liquid must be gathered. In the pharmaceutical industry, comprehensive extractables studies are required for contact materials, and the data is used in the qualification of the process equipment. PES is generated via polycondensation, which forms cyclic oligomers as a by-product of the reaction. However, no structural information is available for these cyclic oligomers so far. In this publication, we present the analytical determination of PES cyclic oligomers. Their presence in extracts of PES membrane filters is confirmed. The structure of the PES cyclic trimer is elucidated by X-ray and NMR investigation, obtained as crystals from the sublimation of the PES raw material. A strategy is shown to assess the toxicity of such cyclic oligomers and to derive a permitted daily exposure (PDE). The data will reduce the levels of unknowns in extractables and leachables screenings and supports the risk assessment of PES sterile filters.
https://doi.org/10.1002/pen.26064
Prestine C60 fullerene as a novel agent in sonodynamic treatment of cancer cells. - In: FEBS Open Bio, ISSN 2211-5463, Bd. 12 (2022), S. 74
https://doi.org/10.1002/2211-5463.13440
Four-level structural hierarchy: microfluidically supported synthesis of polymer particle architectures incorporating fluorescence-labeled components and metal nanoparticles. - In: Langmuir, ISSN 1520-5827, Bd. 38 (2022), 29, S. 8794-8804
Hierarchical assemblies of functional polymer particles are promising due to their surface as well as physicochemical properties. However, hierarchical composites are complex and challenging to form due to the many steps necessary for integrating different components into one system. Highly structured four-level composite particles were formed in a four-step process. First of all, gold (Au) nanoparticles, poly(methyl methacrylate) (PMMA) nanoparticles, and poly(tripropylene glycol diacrylate) (poly-TPGDA) microparticles were individually synthesized. By applying microfluidic techniques, polymer nano- and microparticles were formed with tunable size and surface properties. Afterwards, the negatively charged gold nanoparticles and PMMA particles functionalized with a positively charged surface were mixed to form Au/PMMA assemblies. The Au/PMMA composites were mixed and incubated with poly-TPGDA microparticles to form ternary Au/PMMA/poly-TPGDA assemblies. For the formation of composite-containing microparticles, Au/PMMA/poly-TPGDA composites were dispersed in an aqueous acrylamide-methylenebisacrylamide solution. Monomer droplets were formed in a co-flow microfluidic device and photopolymerized by UV light. In this way, hierarchically structured four-level composites consisting of four different size ranges - 0.025/0.8/30/1000 μm - were obtained. By functionalizing polymer nano- and microparticles with different fluorescent dyes, it was possible to visualize the same composite particle under two different excitation modes (λex = 395-440 and λex = 510-560 nm). The Au/PMMA/poly-TPGDA composite-embedded polyacrylamide microparticles can be potentially used as a model for the creation of composite particles for sensing, catalysis, multilabeling, and biomedical applications.
https://doi.org/10.1021/acs.langmuir.2c00686
PPDN and NTCDA radical anions formation in EMIM-DCA, BMIM-BF4 EMIM-Ac ionic liquid solutions under the steady state UV and Vis light illumination: a combined X-, K-band EPR and DFT study. - In: Journal of molecular liquids, ISSN 1873-3166, Bd. 362 (2022), 119631
The radical anion of Pyrazino[2,3-f][1,10]phenanthroline-2,3-dicarbonitrile (PPDN) in blends with imidazolium based room temperature ionic liquids (RTIL): EMIM-DCA, BMIM-BF4, EMIM-Ac has been detected by X-band continues wave (CW) electron paramagnetic resonance (EPR) under steady state Xe-lamp illumination in the temperature interval from 190 to 340 K. The radical anion of 1,4,5,8-Naphthalenetetracarboxylic dianhydride (NTCDA) was registered by X- and K-band CW EPR at room temperature under the visible light CW diode laser operated at 532 nm, and Xe-lamp as well. The experimental hyperfine coupling data of both anion radicals were confirmed by DFT calculation. The formation of PPDN•- NTCDA•- and fullerene derivative (FD) radical anions is attributed to the photoelectron transfer from an IL anion to PPDN, NTCDA and FD electron acceptors. Here, the electron transfer leads to an irreversibility of these reactions due to photo-induced decomposition of the IL anions in the presence of an effective electron acceptor and is supported in the above RTILs solutions by means of EPR. For the indirect confirmation of the EMIM-DCA, EMIM-AC, BMIM-BF4 anion degradation in solutions with PPDN and NTCDA up to the transient radical state, similar data of acetate anion [OCOCH3]- decomposition, under CW Xe-Lamp photolysis resulting in •CH3 formation and its stabilization at 77 K in EMIM-Ac suspension with some FD dissolved in DCB are introduced as well. However, the main goal of this study is dedicated to the features of rotational and translational diffusion kinetics of PPDN and NTCDA radical anions in IL solutions as well to the evaluation of their application as a spin probes in ILs study in liquid phase.
https://doi.org/10.1016/j.molliq.2022.119631
Novel whitlockite/alginate/C60 fullerene composites: synthesis, characterization and properties for medical application. - In: The Arabian journal for science and engineering, ISSN 2191-4281, Bd. 47 (2022), 6, S. 7093-7104
The hybrid composite materials in form of spheres based on whitlockite-related calcium phosphate, Alginate (20, 30 or 50 wt.%) and C60 Fullerene (C60; 2 or 5 wt.%) were fabricated. According to XRD, elemental analysis and SEM data, the whitlockite-related (hexagonal system, space group R3c) calcium phosphate containing 0.42 wt.% of sodium was obtained in the form of particles with size 50-80 nm. It has been found that the addition of Alginate (20 wt.%) to prepared calcium phosphate leads to an increase in the compressive strength of composite by two times (from 137 to 358 MPa), and value of Young's modulus on 20% (from 460 to 558 MPa), while the presence of C60 in composition did not significant influence on this characteristic. The antibacterial activity of prepared composites with different composition and amounts (2.5, 5 or 10 mM) against Lactobacillus rhamnosus, Lactobacillus salivarius, Staphylococcus aureus and Pseudomonas aeruginosa was studied. All prepared samples did not effect on Lactobacillus. The addition of 5 wt.% C60 to phosphate-Alginate (30 wt.%) composite resulted in a tenfold decrease in the survival rate of the S. aureus strain at 5 and 10 mM of samples while P. aeruginosa was less sensitive to action of this sample and inhibition of bacteria growth was occurred only at its amount 10 mM. Thus, the results of mechanical properties and impact of created nanostructured hybrid composites on normal human microbiota (Lactobacillus) as well as pathogenic strain (S. aureus and P. aeruginosa) indicate the suitability of these promising materials for further biological test for bone therapy.
https://doi.org/10.1007/s13369-021-06552-0
Analysis of biomechanical and biochemical markers of rat muscle soleus fatigue processes development during long-term use of C60 fullerene and N-acetylcysteine. - In: Nanomaterials, ISSN 2079-4991, Bd. 12 (2022), 9, 1552, S. 1-15
The development of an effective therapy aimed at restoring muscle dysfunctions in clinical and sports medicine, as well as optimizing working activity in general remains an urgent task today. Modern nanobiotechnologies are able to solve many clinical and social health problems, in particular, they offer new therapeutic approaches using biocompatible and bioavailable nanostructures with specific bioactivity. Therefore, the nanosized carbon molecule, C60 fullerene, as a powerful antioxidant, is very attractive. In this study, a comparative analysis of the dynamic of muscle soleus fatigue processes in rats was conducted using 50 Hz stimulation for 5 s with three consistent pools after intraperitoneal administration of the following antioxidants: C60 fullerene (a daily dose of 1 mg/kg one hour prior to the start of the experiment) and N-acetylcysteine (NAC; a daily dose of 150 mg/kg one hour prior to the start of the experiment) during five days. Changes in the integrated power of muscle contraction, levels of the maximum and minimum contraction force generation, time of reduction of the contraction force by 50% of its maximum value, achievement of the maximum force response, and delay of the beginning of a single contraction force response were analyzed as biomechanical markers of fatigue processes. Levels of creatinine, creatine phosphokinase, lactate, and lactate dehydrogenase, as well as pro- and antioxidant balance (thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione, and catalase activity) in the blood of rats were analyzed as biochemical markers of fatigue processes. The obtained data indicate that applied therapeutic drugs have the most significant effects on the 2nd and especially the 3rd stimulation pools. Thus, the application of C60 fullerene has a (50-80)% stronger effect on the resumption of muscle biomechanics after the beginning of fatigue than NAC on the first day of the experiment. There is a clear trend toward a positive change in all studied biochemical parameters by about (12-15)% after therapeutic administration of NAC and by (20-25)% after using C60 fullerene throughout the experiment. These findings demonstrate the promise of using C60 fullerenes as potential therapeutic nanoagents that can reduce or adjust the pathological conditions of the muscular system that occur during fatigue processes in skeletal muscles.
https://doi.org/10.3390/nano12091552
Effect of fullerene C60 thermal and tribomechanical loading on Raman signals. - In: Diamond and related materials, ISSN 0925-9635, Bd. 126 (2022), 109036, S. 1-14
Fullerene C60 powder was loaded by 1 N normal force and exposed to sliding under different frequencies for 15 min. It is shown that the velocity of the sliding movement determines the stability of the fullerene C60 powder. At slow velocity of movement with a frequency of 1 Hz under 1 N normal force, the fullerene C60 structure remains undamaged after 15 min sliding. On the contrary, high sliding velocities of 10 Hz and 50 Hz affected fragmentation of the fullerene C60, which resulted in a reduction of the coefficient of friction (COF). During sliding with 1 Hz, the friction reached the highest level with an average COF of 0.59 ± 0.03. The faster relative motion under 1 N normal force gave a lower average COF with 0.39 ± 0.03. The initial fullerene C60 powder formed a thick compressed layer in the tribomechanical loaded zone. As proven by Raman spectroscopy, operating the tribomechanical sliding test at 50 Hz stimulated the re-attraction of fresh C60 fullerene island onto the fragmented layer from outside of the loaded powder regions. The COF was increasing again up to 0.44 ± 0.04 for 1 N normal force and 50 Hz frequency. The fragmentation and decomposition of fullerene C60 with increasing sliding velocity is attributed to thermal heating up during fast relative movement. Raman spectra of the tribomechanical loaded fullerene C60 are compared with Raman spectra from slowly heated up C60 in air and with Raman spectra of laser irradiated fullerene C60.
https://doi.org/10.1016/j.diamond.2022.109036
Post-traumatic recovery of muscle soleus in rats is improved via synergistic effect of C60 fullerene and TRPM8 agonist menthol. - In: Applied nanoscience, ISSN 2190-5517, Bd. 12 (2022), 3, S. 467-478
Functional biomechanical parameters of muscle soleus contraction in rats as well as selected blood biochemical parameters were studied during the first 3 days of post-traumatic syndrome progression caused by the destruction of muscle cells by compression. Single administration of the antioxidant C60 fullerene and the selective agonist of TRPM8 channels menthol were used as therapeutic agents. Injection of C60 fullerene at a concentration of 1 mg/kg into the damaged muscle improved its contractile function by 25-28%. The use of combined injections of C60 fullerene and menthol (at the concentration 1 mg/kg) improved this index by additional 27-39% and simultaneously stabilized the decrease in muscle strength observed throughout the experiment. A tendency towards a decrease in the indexes of the above described biochemical parameters by 10-15% were found with the therapeutic administration of C60 fullerene. With combined injections of C60 fullerene and menthol, the above described biochemical parameters decreased by an additional 17-24%. The synergism between the action of menthol and C60 fullerene on the post-traumatic recovery of skeletal muscle function opens up new perspectives for the clinical application of this combination therapy.
https://doi.org/10.1007/s13204-021-01703-z
Effect of C60 fullerene on recovery of muscle soleus in rats after atrophy induced by achillotenotomy. - In: Life, ISSN 2075-1729, Bd. 12 (2022), 3, 332, S. 1-13
Biomechanical and biochemical changes in the muscle soleus of rats during imitation of hind limbs unuse were studied in the model of the Achilles tendon rupture (Achillotenotomy). Oral administration of water-soluble C60 fullerene at a dose of 1 mg/kg was used as a therapeutic agent throughout the experiment. Changes in the force of contraction and the integrated power of the muscle, the time to reach the maximum force response, the mechanics of fatigue processes development, in particular, the transition from dentate to smooth tetanus, as well as the levels of pro- and antioxidant balance in the blood of rats on days 15, 30 and 45 after injury were described. The obtained results indicate a promising prospect for C60 fullerene use as a powerful antioxidant for reducing and correcting pathological conditions of the muscular system arising from skeletal muscle atrophy.
https://doi.org/10.3390/life12030332
A novel water-soluble C60 fullerene-based nano-platform enhances efficiency of anticancer chemotherapy. - In: Biomedical nanomaterials, (2022), S. 59-93
Im Titel ist "60" tiefgestellt
Noncovalent water-soluble nanocomplexes of C60 fullerene (C60) with chemotherapeutic drugs (Doxorubicin (Dox), Cisplatin (Cis), and herbal alkaloid Berberine (Ber)) were created. Their anticancer action toward various tumor cells was studied in vitro, addressing specifically their biological synergy, compared with the action of these drugs in the non-immobilized form. Different theoretical and experimental (SEM and AFM microscopy, UV-Vis, DLS, NMR and SANS spectroscopy, ITC calorimetry) methods were applied for getting insight into the nature of the nanocomplexes with drug molecules, as well as into the physical forces enabling stabilization of these complexes. Physicochemical mechanisms were proposed for drug interaction with C60. An enhancement of the toxic action of the created water-soluble C60-drug nanocomplexes toward cancer cells, compared to the action of free drug, was found. Specifically, the C60-Dox nanocomplexes demonstrated ˜3.5 higher cytotoxic potential in the leukemic cell lines (CCRF-CEM, Jurkat, THP1, and Molt-16) in comparison with free Dox in the nanometer range of concentrations. Besides, C60 doubled the intracellular level of the up-taken Dox, which also evidenced its function as a nanocarrier. The toxic effect of C60-Cis nanocomplex toward Lewis lung carcinoma (LLC) cells was shown to be higher with IC50 values 3.3 and 4.5 times at 48 h and 72 h, respectively, as compared to the IC50 of free drug. 12.5 [my] Cis had no effect on LLC cells' viability. The C60-Cis nanocomplex in Cis-equivalent concentration substantially decreased the viability of tumor cells, impaired their shape and adhesion, inhibited migration, and induced their accumulation in the pro-apoptotic sub-G1 phase of cell cycle. An induction of apoptosis by the C60-Cis nanocomplex was confirmed by the activation of caspase 3/7 and externalization of phosphatidylserine on the outer membrane of LLC cells after their double staining with the Annexin V-FITC/PI. The complexation with C60 promoted intracellular uptake of the Ber. An increase in C60 concentration in the C60-Ber nanocomplexes was accompanied by the elevation of their antiproliferative potential toward CCRF-CEM cells in the order: free Ber < 1:2 < 1:1 < 2:1.These findings suggest a universal potential of water-soluble pristine C60 as a unique nano-platform for the delivery of the chemotherapeutic drugs in cytotoxic effect of these drugs.