Beyond graphene oxide: Laser engineering functionalized graphene for flexible electronics

Carbon nanomaterials, especially graphene, are promising due to their abundance and the possibility to exploit them in lightweight, flexible, and wearable electronics enabling paradigms such as the Internet of Things. However, conventional methods to synthesize and integrate graphene into functional materials and flexible devices are either hazardous, time demanding, or excessively energy-consuming. To overcome these issues, here we propose a new concept based on the laser processing of single-layer diazonium-functionalized graphene. This is a safe, inexpensive, and environmentally-friendly method making it a competitive alternative for graphene-device fabrication. Flexible chemiresistors exhibit sensitivity for breath (water vapor and CO2) and ethanol detection up to 1500% higher than laser-reduced graphene oxide devices. We attribute this enhanced sensitivity to an optimal balance between structural defects and electrical conductivity. Flexible electronic circuits demonstrate a superb resilience against scratching and high current stability up to 98% with durability against 180° bending cycles for continuous operation of several weeks. This work can impact biomedical technology and electronics where tunable electrical conductivity, sensitivity, and mechanical stability are of uttermost importance. © 2020 The Royal Society of Chemistry

Cerebellar dysfunction in multiple sclerosis

International audienceThe optimization of a palladium-catalyzed Heck Matsuda reaction using an optimization algorithm is presented. We modified and implemented the Nelder-Mead method in order to perform constrained optimizations in a multidimensional space. We illustrated the power of our modified algorithm through the optimization of a multivariable reaction involving the arylation of a deactivated olefin with an arenediazonium salt. The great flexibility of our optimization method allows to fine-tune experimental conditions according to three different objective functions: maximum yield, highest throughput, and lowest production cost. The beneficial properties of flow reactors associated with the power of intelligent algorithms for the fine-tuning of experimental parameters allowed the reaction to proceed in astonishingly simple conditions unable to promote the coupling through traditional batch chemistry

Branched poly (lactic acid) microparticles for enhancing the 5-aminolevulinic acid phototoxicity

An innovative microcarrier based on a carboxy-enriched and branched polylactic acid derivative was developed to enhance the in vitro phototoxicity of the photosensitizer and prodrug 5-aminolevulinic. Microparticles, prepared by double emulsion technique and loaded with the prodrug were carefully characterized and the effect of the polymer structure on the chemical, physical and biological properties of the final product was evaluated. Results showed that microparticles have a spherical shape and ability to allocate up to 30 μg of the photosensitizer per mg of carrier despite their difference in solubility. Release studies performed in various simulated physiological conditions demonstrate the influence of the branched structure and the presence of the additional carboxylic groups on the release rate and the possibility to modulate it. In vitro assays conducted on human epithelial adenocarcinoma cells proved the not cytotoxicity of the carriers in a wide range of concentrations. The hemocompatibility and surface proteins adsorption were evaluated at different microparticles concentrations to evaluate the safety and estimate the possible microparticles residential time in the bloodstream. The advantages, of loading 5-aminolevulinic acid in the prepared carrier has been deeply described in terms of enhanced phototoxicity, compared to the free 5-aminolevulinic acid formulation after irradiation with light at 635 nm. The obtained results demonstrate the advantages of the prepared derivative compared to the linear polylactide for future application in photodynamic therapy based on the photosensitizer 5-aminolevulinic acid. © 2018 Elsevier B.V.CZ.1.05/2.1.00/19.0409, MŠMT, Ministerstvo Školství, Mládeže a Tělovýchovy; LO1504, MŠMT, Ministerstvo Školství, Mládeže a TělovýchovyCzech Ministry of Education, Youth and Sports [LO1504, CZ.1.05/2.1.00/19.0409]; Tomsk Polytechnic University [VIU-316/2017

Enhancement of the antioxidant activity and stability of β-carotene using amphiphilic chitosan/nucleic acid polyplexes

β-carotene is a natural compound with significant antioxidant activity. However, its poor solubility in water and low stability reduce its potential application. Innovative polyplexes based on the combination of amphiphilic chitosan assembled with DNA have been developed using a solvent-free, simple and low-cost method with the aim to load, retain and enhance the antioxidant capability of β-carotene. The polyplexes, with dimension about 100 nm, and excellent stability, were able to hold up to 400 μg of β-carotene per mg of the carrier, with minimal loss till two weeks. The antioxidant activity was significantly enhanced after loading, as demonstrated using two well known methods. Cytotoxicity assay confirmed the not toxicity of the system. The results suggest the polyplexes as an excellent candidate to develop formulation able to preserve and enhance the peculiarities of compounds which are used mainly in food, cosmetic and pharmaceutic but with still some limitations. © 2018VIU-RSCABS-89/2018, TPU, Tomsk Polytechnic University; NPU I LO1504Ministry of Education, Youth and Sports of the Czech Republic [NPU I LO1504]; Tomsk Polytechnic University [VIU-RSCABS-89/2018

Polysaccharides based microspheres for multiple encapsulations and simultaneous release of proteases

The work is focused on the development of microspheres based on the combination of two polysaccharides; chitosan and alginic acid with the aim to allocate, hold, release and protect environmentally sensible molecules. The microspheres were prepared using a solvent-free, low cost and scalable approach and two enzymes; trypsin and protease from Aspergillus Oryzae have been used as a model to evaluate the microspheres peculiarities. The proteins were encapsulated during the microspheres preparation. The relationship between the polysaccharides weight ratio and the morphology, stability and ability of the carrier to allocate the enzymes has been evaluated. The enzymatic activity and the release kinetics were assessed in different conditions to assess the impact of the external environment. Obtained results demonstrate the efficacy of the prepared microspheres to preserve the activity of relevant bioactive compounds which are highly relevant in food, cosmetic and pharmaceutic, but the application is limited due to their high sensibility. © 2019 Elsevier B.V.Ministry of Education, Youth and Sports of the Czech Republic; NPU [LO1504]; Tomsk Polytechnic University [VIU-RSCABS-89/2018

Multidrug delivery system based on polysaccharide nanocomplexes for controlled delivery of a combination of chemotherapeutics

Development of delivery systems able to hold and release a combination of bioactive compounds at the target site represents a strategy for improving the therapeutic outcomes and overcome the central issues in the multitherapeutic approach. A delivery system based on polysaccharides suitable for loading a combination of chemotherapeutic drugs, doxorubicin and 5-fluorouracil, at defined weight ratio and deliver them following a pH-dependent kinetics was developed. Nanocomplexes were prepared by polyelectrolytes complexation and characterised in terms of average dimension, morphology, drug content by dynamic light scattering, transmission and scanning microscope and UV–Vis spectroscopy, respectively. The complexes showed a spherical shape with the hydrodynamic diameter between 100 and 130 nm, positive ς-potential, high stability in physiological environment and up to 800 μg of drugs per mg loaded. Release studies demonstrate a pH-dependent trend with high control of the release rate for each compound. In vitro hemocompatibility and not cytotoxicity were observed. In vitro studies showed a significate reduction of the cell viability after contact with the dual-drug loaded complexes than the single-loaded and free-drug formulations demonstrating the synergic effect of the drugs and the advantages of using the complexes. The results show the potential application of the nanosystems for multiple-drug delivery in therapy. © 2019 Elsevier B.V.Tomsk Polytechnic University [VIU-RSCABS-89/2018]; Ministry of Education, Youth and Sports of the Czech Republic; NPU [LO1504

Organic-inorganic hybrid nanoparticles controlled delivery system for anticancer drugs

The use of organic-inorganic hybrid nanocarriers for controlled release of anticancer drugs has been gained a great interest, in particular, to improve the selectivity and efficacy of the drugs. In this study, iron oxide nanoparticles were prepared then surface modified via diazonium chemistry and coated with chitosan, and its derivative chitosan-grafted polylactic acid. The purpose was to increase the stability of the nanoparticles in physiological solution, heighten drug-loading capacity, prolong the release, reduce the initial burst effect and improve in vitro cytotoxicity of the model drug doxorubicin. The materials were characterized by DLS, ζ-potential, SEM, TGA, magnetization curves and release kinetics studies. Results confirmed the spherical shape, the presence of the coat and the advantages of using chitosan, particularly its amphiphilic derivative, as a coating agent, thereby surpassing the qualities of simple iron oxide nanoparticles. The coated nanoparticles exhibited great stability and high encapsulation efficiency for doxorubicin, at over 500 μg per mg of carrier. Moreover, the intensity of the initial burst was clearly diminished after coating, hence represents an advantage of using the hybrid system over simple iron oxide nanoparticles. Cytotoxicity studies demonstrate the increase in cytotoxicity of doxorubicin when loaded in nanoparticles, indirectly proving the role played by the carrier and its surface properties in cell uptake. © 2017 Elsevier B.V.Czech Science Foundation [15-08287Y]; Ministry of Education, Youth and Sports of the Czech Republic [LO1504, CZ.1.05/2.1.00/19.0409]; RFBR [16-33-00351

Matsuda–Heck reaction with arenediazonium tosylates in water

An environmentally friendly Matsuda–Heck reaction with arenediazonium tosylates has been developed for the first time. A range of alkenes was arylated in good to quantitative yields in water. The reaction is significantly accelerated when carried out under microwave heating. The arylation of haloalkylacrylates with diazonium salts has been implemented for the first time

Chitosan-collagen based film for controlled delivery of a combination of short life anesthetics

The present research was undertaken to develop a chitosan-collagen film for controlled delivery of combinations of local anesthetics. The film has been prepared by casting which is a versatile, rapid and low-cost approach distinguished by high reproducibility. The mechanical, morphological, and physicochemical properties of the films and the impact of the drug loading were evaluated. We showed that the formulations have a good combination of strength and flexibility with high water permeability. Surface morphology investigation indicates a variation in roughness depending on the loaded compound. Release studies were performed in controlled environments and the data processed by the Higuchi model to assess the dynamics of the release. The local anesthetics, lidocaine, tetracaine, and benzocaine, were uniformly distributed within the matrix and released in a rate and magnitude specific for the drug concentration and combination tunable in a range time from 6 h to 24 h. The films dissolve completely in the physiological environment within 24 h without leaving any toxic metabolites as both of the components are recognized as safe. In vitro cytotoxicity and cell proliferation tests performed on human dermal fibroblast demonstrate the biocompatibility and lack of cytotoxicity of the prepared formulations. © 2019 Elsevier B.V.Ministry of Education, Youth and Sports of the Czech RepublicMinistry of Education, Youth & Sports - Czech Republic [L01504]; Tomsk Polytechnic University [VIU-RSCABS-68/2019