Membranotropic and Antiradical Properties of 2-Nitroxysuccinate 3-Hydroxy-6-Methyl-2-Ethylpyridine.

We studied membranotropic properties of NO donor 2-nitroxysuccinate 3-hydroxy-6-methyl-2-ethylpyridine and its structural analog succinate 3-hydroxy-6-methyl-2-ethylpyridine (Mexidol). It was shown that the compounds under study are incorporated into modeled membranes and form long-living complexes with pyrene in the region of fatty acid tails of phospholipids. Luminol-amplified chemiluminescence analysis showed that both compounds exhibited antiradical activity and in a concentration of 0.1 mM reduced chemiluminescence intensity by more than 70%. 2-Nitroxysuccinate 3-hydroxy-6-methyl-2-ethylpyridine inhibited catalytic activity of monoamine oxidase A more efficiently than its structural analogue Mexidol.

Experimental and Theoretical Study on the Synergistic Inhibition Effect of Pyridine Derivatives and Sulfur-Containing Compounds on the Corrosion of Carbon Steel in CO2-Saturated 3.5 wt.% NaCl Solution.

The corrosion inhibition performance of pyridine derivatives (4-methylpyridine and its quaternary ammonium salts) and sulfur-containing compounds (thiourea and mercaptoethanol) with different molar ratios on carbon steel in CO2-saturated 3.5 wt.% NaCl solution was investigated by weight loss, potentiodynamic polarization, electrochemical impedance spectroscopy, and scanning electron microscopy. The synergistic corrosion inhibition mechanism of mixed inhibitors was elucidated by the theoretical calculation and simulation. The molecules of pyridine derivative compounds with a larger volume has priority to adsorb on the metal surface, while the molecules of sulfur-containing compounds with a smaller volume fill in vacancies. A dense adsorption film would be formed when 4-PQ and sulfur-containing compounds are added at a proper mole ratio.

Non-Covalent Assembly Method that Simultaneously Endows a Liposome Surface with Targeting Ligands, Protective PEG Chains, and Deep-Red Fluorescence Reporter Groups.

A new self-assembly method is used to rapidly functionalize the surface of liposomes without perturbing the membrane integrity or causing leakage of the aqueous contents. The key molecule is a cholesterol-squaraine-PEG conjugate with three important structural elements: a cholesterol membrane anchor, a fluorescent squaraine docking station that allows rapid and high-affinity macrocycle threading, and a long PEG-2000 chain to provide steric shielding of the decorated liposome. The two-step method involves spontaneous insertion of the conjugate into the outer leaflet of pre-formed liposomes followed by squaraine threading with a tetralactam macrocycle that has appended targeting ligands. A macrocycle with six carboxylates permitted immobilization of intact fluorescent liposomes on the surface of cationic polymer beads, whereas a macrocycle with six zinc(II)-dipicolylamine units enabled selective targeting of anionic membranes, including agglutination of bacteria in the presence of human cells.

[DYNAMICS OF BACTERIOLOGICAL AND PLANIMETRIC INDICES OF THE WOUND UNDER THE ACTION OF THE SILVER NANOPARTICLES, STABILIZED BY MEXIDOL AND POLYVINYLPYRROLIDONE].

Changes in bacteriological indices through the square of the wound of chemical origin under local impact of the silver nanoparticles (NP), stabilized by 2-ethyl-6-methyl-3-hydroxypyridine succinate (mexidol) and polyvinylpyrrolidone were studied. The wounds of submandibular region were simulated in white rats, using injection of 10% solution of calcium chloride with further opening of necrotic foci and open management of the wound. Beginning from the fifth day, every day the wound was irrigated with liquid, which have contented the stabilized NP of the silver, 0.05% water solution of chlorhexidine or isotonic solution of the the sodium chloride (control). There was established, that the silver NP impact antiseptically and regenerative while the wound treatment, and reduce during 10 days microbial contamination of exudate in 24 times, the wound square--in three times in comparison with original indices. These changes were identical to those while application of chlorhexidine.

Robust superbase-based emerging solvents for highly efficient dissolution of cellulose.

The development of robust solvent systems for cellulose dissolution is of significant importance for cellulose utilization and transformation. Herein, six kinds of novel superbase-based solvents were designed by a combination of 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) with pyridine N-oxide (PyO) or 2-picoline-N-oxide (PiO) for dissolution of cellulose. It was observed that the prepared superbase-based solvents (denoted as DBN-PyO-x and DBN-PiO-4) could efficiently dissolve cellulose at mild temperatures (<80 °C). The chemical structure of the prepared superbase-based solvents and the molar ratio of the components significantly affected the solubility of cellulose, and DBN-PyO-4 showed the best performance with a cellulose solubility of 14.1 wt% 70 °C. The systematic study revealed that the good performance of the prepared superbase-based solvents on cellulose dissolution resulted from the synergistic effect of their ability to form hydrogen bonds and their polarizability.

Zinc(II)-Dipicolylamine Analogs Mediated PEI1.8k/pDNA Vector: Effect of Ligand Structure on the Gene Transport Process.

Zinc ion complexes of dipicolylamine analogs, due to the strong synergistic effect between the Zn2+ complex of containing polypyridine derivatives and polycations in each key step of pDNA transport, have been used as the third component to mediate polyethyleneimine with molecular weight 1.8 kDa (PEI1.8k)/DNA gene delivery system. And the effects of different structural characteristics, such as the number of pyridinamine ligands, the hydrophilic-hydrophobicity of the adjacent groups, on the in vitro transfection performance of the ternary complex are systematically investigated. This ternary hybrid system provides an effective strategy to improve the gene delivery of cationic polymers.

Pharmaceutical-grade oral films as substrates for printed medicine.

In contact-less printing, such as piezo-electric drop on demand printing used in the study, the drop formation process is independent of the substrate. This means that having developed a printable formulation, printed pharmaceutical dosage forms can be obtained on any pharmaceutical grade substrate, such as polymer-based films. In this work we evaluated eight different oral films based on their suitability as printing substrates for sodium picosulfate. The different polymer films were compared regarding printed spot morphology, chemical stability and dissolution profile. The morphology of printed sodium picosulfate was investigated with scanning electron microscopy and optical coherence tomography. The spreading of the deposited drops was found to be governed by the contact angle of the ink with the substrate. The form of the sodium picosulfate drops changed on microcrystalline cellulose films at ambient conditions over 8 weeks and stayed unchanged on other tested substrates. Sodium picosulfate remained amorphous on all substrates according to small and wide angle X-ray scattering, differential scanning calorimetry and polarized light microscopy measurements. The absence of chemical interactions between the drug and substrates, as indicated by infrared spectroscopy, makes all tested substrates suitable for printing sodium picosulfate onto them.

[Role of mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) in the obtaining of stabilized magnetite nanoparticles for biomedical application].

Magnetite nanoparticles (NPs) are studied as agents for magnetic resonance imaging, hyperthermia of malignant tumors, targeted drug delivery as well as anti-anemic action. One of the main problems of such NPs is their aggregation that requires creation of methods for magnetite NPs stabilization during preparation of liquid medicinal forms on their basis. The present work is devoted to the possibility of mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) use for solubilization of magnetite NPs in hydrophilic medium. For this purpose, the condensate produced by electron-beam evaporation and condensation, with magnetite particles of size 5-8 nm deposited into the crystals of sodium chloride were used in conjunction with substance of mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), and low molecular weight polyvinylpyrrolidone (PVP). The NP condensate was dispersed in distilled water or PVP or mexidol solutions. NPs size distribution in the liquid phase of the systems was determined by photon correlation spectroscopy, iron (Fe) concentration was evaluated by atomic emission spectrometry. It is shown that in the dispersion prepared in distilled water, the major amount of NPs was of 13-120 nm in size, in mexidol solution - 270-1700 nm, in PVP solution - 30-900 nm. In the fluid containing magnetite NPs together with mexidol and PVP, the main fraction (99.9%) was characterized by the NPs size of 14-75 nm with maximum of 25 nm. This system had the highest iron concentration: it was similar to that in the sample with mexidol solution and 6.6-7.3 times higher than the concentration in the samples with distilled water or PVP. Thus, in the preparation of aqueous dispersions based on magnetite NPs condensate, mexidol provides a transition of Fe to the liquid phase in amount necessary to achieve its biological activity, and PVP stabilizes such modified NPs.

[Antioxidant activity of inhibitors of free radical reactions in the dressing materials for wound healing].

Antioxidant activity (AA) of inhibitors of free radical reactions (FRR) (dieton, mexidol, trypsin), aplied to the dressing material for wound healing was studied. In our work we used a model system containing suspension of laminated liposome, formed from fraction of total chicken yolk phospholipids. Lipid peroxidation (LPO) of liposome membranes was initiated by addition of Fe2+ ions. The kinetics of FRR was followed by coumarine-enhanced chemiluminescence (CL). It was found that AA of the inhibitors was determined by their ability to intersept aqueous and hydrofobic free radicals and chelate Fe2+ ions. Their ability to intersept radicals reduced in the following order: dieton > trypsin > mexidol. In addition we discovered unknown ability of mexidol to interact with Fe2+, that resulted in elemination of FRR catalyst. Investigating AA of the FRR inhibitors in the two-components mixture, consisting of dieton and mexidol, we observed the effect of multifunctionality: dieton, increased the duration of latent period of CL by intersepting lipid peroxyl radicals, while mexidol, decreased its value by interacting with Fe2+, i.e. mexidol masked the action of dieton. Investigating AA of two-components mixture, consisting of mexidol and trypsine, we observed the same effect of multifunctionality. In the two-component mixture, consisting of trypsine and dieton, the action of the inhibitors was found to be synergistic. All antioxidant properties of these FRR inhibitors were also preserved in the three component mixture. Hence, mixture components, dieton, mexidol and trypsin, possess high AA, that validates their use in dressing materials employed for wound healing.

Sunfish cationic amphiphiles: toward an adaptative lipoplex morphology.

A detailed physicochemical study is presented on a new class of cationic amphiphiles, Sunfish amphiphiles, recently designed, synthesized, and tested for gene delivery. These materials have two hydrophobic tails, connected to the cationic pyridinium headgroup at the 1- and 4-positions. Two extreme morphologies can be visualized, i.e. one by back-folding involving association of both tails at one side of the pyridinium ring and one by independent unfolding of the tails, the two molecular geometries leading to considerable differences in the aggregate morphology. The behavior of six members of the Sunfish family in mixtures with DOPE, applying different conditions relevant for transfection, has been studied by a combination of techniques (DLS, DSC, NMR, SAXS, Cryo-TEM, fluorescence, etc.). The effects of structural parameters such as the presence of unsaturation in the tails and length of the alkyl chains on the properties of the aggregates have been assessed. A correlation of these structural data with cellular transfection efficiencies reveals that the highest transfection efficiency is obtained with those amphiphiles that are easily hydrated, form fluid aggregates, and undergo a transition to the inverted hexagonal phase in the presence of plasmid DNA (p-DNA) at physiological ionic strength.