Photopolymerized thermosensitive poly(HPMAlactate)-PEG-based hydrogels : effect of network design on mechanical properties, degradation, and release behavior

Photopolymerized thermosensitive A-B-A triblock copolymer hydrogels composed of poly(N-(2-hydroxypropyl)-methacrylamide lactate) A-blocks, partly derivatizal with methacrylate groups to different extents (10, 20, and 30%) and hydrophilic poly(ethylene glycol) B-blocks of different molecular weights (4, 10, and 20 kDa) were synthesized. The aim of the present study was to correlate the polymer architecture with the hydrogel properties, particularly rheological, swelling, degradation properties and release behavior. It was found that an increasing methacrylation extent and a decreasing PEG molecular weight resulted in increasing gel strength and cross-link density, which tailored the degradation profiles from 25 to more than 300 days. Polymers having small PEG blocks showed a remarkable phase separation into polymer- and water-rich domains, as demonstrated by confocal microscopy. Depending on the hydrophobic domain density, the loaded protein resides in the hydrophilic pores or is partitioned into hydrophilic and hydrophobic domains, and its release from these compartments is tailored by the extent of methacrylation and by PEG length, respectively. As the mechanical properties, degradation, and release profiles can be fully controlled by polymer design and concentration, these hydrogels are suitable for controlled protein release

Соціальна культура громадян - найкращий антикризовий засіб

An anthracene-functionalized thermosensitive block copolymer was synthesized, which formed micelles by heating its aqueous solution above the lower critical solution temperature (LCST). The micelles were subsequently crosslinked by UV illumination at 365 nm with a normal handheld UV lamp. The micelles showed a small size (30 nm) and high loading capacity (16.0 ± 0.1%) for paclitaxel and released paclitaxel for more than ten days

Инструментарий минимизации риска защищенности в распределенных системах (РКС)

Разработана структура средств минимизации риска защищенности распределенных компьютерных систем, выполнена формализация функционирования основных блоков предложенной структуры. Предложена оценка уровня угроз безопасности, интегральная оценка ущерба вследствие атак на уязвимости, а также оценка степени риска реализации угроз безопасности в компьютерных системах. Также предложен подход к анализу риска на основе оценок степени опасности факторов угроз безопасности и вероятности реализации угроз безопасности с разделением их на соответствующие группы, а также на основе построения специальной матрицы рисков защищенности для минимизации риска защищенности.Розроблено структуру засобів мінімізації ризику захищеності розподілених комп’ютерних систем, виконано формалізацію функціонування основних блоків запропонованої структури. Запропоновано оцінку рівня загроз безпеки, інтегральну оцінку збитку внаслідок атак на вразливості, а також оцінку ступеня ризику реалізації загроз безпеки в комп’ютерних системах. Також запропоновано підхід до аналізу ризику на основі оцінок ступеня небезпеки факторів загроз безпеки та ймовірності реалізації загроз безпеки з розділенням їх на відповідні групи, а також на основі побудови спеціальної матриці ризиків захищеності для мінімізації ризику захищеності.The structure of means for security risk minimization in distributed computer systems is developed, and the functioning of the basic blocks of the suggested structure is formalized. Also, estimation of the security threat level, the integrated assessment of the damage due to attacks on to the vulnerabilities, and the risk assessment for the security threat realization are proposed. An approach to the risk analysis on the basis of estimation of the danger level of safety threat factors and the probability of safety threat realization with division of the factors into related groups is suggested, which is also based on the constructed special security risk matrix for security risk minimization

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Этноконфликт как причина агрессии: проблема национальной безопасности Украины

Межэтнические и межнациональные противоречия являются сегодня одной из наиболее актуальных проблем многих стран мира, в том числе и Украины. Она относится к числу полиэтнических государств, где неизбежны межэтнические и межнациональные противоречия и конфликты. Анализу последних, их причин и возможных следствий и посвящена данная статья.Міжетнічні та міжнаціональні протиріччя сьогодні є однією з найбільш актуальних проблем багатьох країн світу, у тому числі і України. Вона належить до числа поліетнічних держав, де неминучі міжетнічні та міжнаціональні протиріччя та конфлікти, аналізу яких, їх причин і можливих наслідків присвячена дана стаття.Today interethnic and international contradictions are the most topical problems of many countries of the world including Ukraine. It belongs to those polyethnic states where interethnic and international contradictions and conflicts are unavoided. This article is devoted to analysis, causes and possible consequences of the last ones

Развитие инвестиционного кредитования в Украине

Free radical polymerization is often used to prepare protein and peptide-loaded hydrogels for the design of controlled release systems and molecular imprinting materials. Peroxodisulfates (ammonium peroxodisulfates (APS) or potassium peroxodisulfates (KPS)) with N,N,N,N-tetramethylethylenediamine (TEMED) are frequently used as initiator and catalyst. However, exposure to these free radical polymerization reagents may lead to modification of the protein and peptide. In this work, we show the modification of lysine residues by ammonium peroxodisulfate (APS)/TEMED of the immunostimulant thymopentin (TP5). Parallel studies on a decapeptide and a library of 15 dipeptides were performed to reveal the mechanism of modification. LC-MS of APS/TEMED-exposed TP5 revealed a major reaction product with an increased mass (+12 Da) with respect to TP5. LC-MS2 and LC-MS3 were performed to obtain structural information on the modified peptide and localize the actual modification site. Interpretation of the obtained data demonstrates the formation of a methylene bridge between the lysine and arginine residue in the presence of TEMED, while replacing TEMED with a sodium bisulfite catalyst did not show this modification. Studies with the other peptides showed that the TEMED radical can induce methyleneation on peptides when lysine is next to arginine, proline, cysteine, aspargine, glutamine, histidine, tyrosine, tryptophan, and aspartic acid residues. Stability of peptides and protein needs to be considered when using APS/TEMED in in situ polymerization systems. The use of an alternative catalyst such as sodium bisulfite may preserve the chemical integrity of peptides during in situ polymerization

Філософія права в системі наук

Thermosensitive amphiphilic block copolymers self-assemble into micelles above their lower critical solution temperature in water, however, the micelles generally display mediocre physical stability. To stabilize such micelles and increase their loading capacity for chemotherapeutic drugs, block copolymers with novel aromatic monomers were synthesized by free radical polymerization of N-(2-benzoyloxypropyl methacrylamide (HPMAm-Bz) or the corresponding naphthoyl analogue (HPMAm-Nt), with N-(2-hydroxypropyl) methacrylamide monolactate, using a polyethylene glycol based macroinitiator. The critical micelle temperatures and critical micelle concentrations decreased with increasing the HPMAm-Bz/Nt content. The micelles of 30-50 nm were prepared by heating the polymer aqueous solutions from 0 to 50 degrees C and were colloidally stable for at least 48 h at pH 7.4 and 37 degrees C. Paclitaxel and docetaxel encapsulation was performed by mixing drug solutions in ethanol with polymer aqueous solutions and heating from 0 to 50 degrees C. The micelles had a drug loading capacity up to 34 wt % for docetaxel, which is among the highest loadings reported for polymeric micelles, with loaded micelle sizes ranging from 60 to 80 nm. The micelles without aromatic groups almost completely released loaded paclitaxel in 10 days, whereas the HPMAm-Bz/Nt containing micelles released 50% of the paclitaxel at the same time, which showed a better retention for the drug of the latter micelles. (1)H solid-state NMR spectroscopy data are compatible with pi-pi stacking between aromatic groups. The empty micelles demonstrated good cytocompatibility, and paclitaxel-loaded micelles showed high cytotoxicity to tumor cells. In conclusion, the pi-pi stacking effect introduced by aromatic groups increases the stability and loading capacity of polymeric micelles

Reaction-diffusion model for the preparation of polymer gratings by patterned ultraviolet illumination

A model is developed to describe the migration mechanism of monomers during the lithographic preparation of polymer gratings by ultraviolet polymerization. The model is based on the Flory–Huggins theory: a thermodynamic theory that deals with monomer/polymer solutions. During the photoinduced polymerization process, monomer migration is assumed to be driven by a gradient in the chemical potential rather than the concentration. If the chemical potential is used as the driving force, monomer migration is not only driven by a difference in concentration, or volume fraction, but also by other entropic effects such as monomer size and the degree of crosslinking of the polymer network, which is related to the ability of a polymer to swell. Interaction of the monomers with each other or the polymer is an additional energetic term in the chemical potential. The theoretical background of the model is explained and results of simulations are compared with those of nuclear microprobe measurements. A nuclear microprobe is used to determine the spatial monomer distribution in the polymer gratings. It is shown that two-way diffusion is expected if the monomers are both difunctional and have the same size. In some cases, if one monomer is considerably smaller than the other, it can eventually have a higher concentration in the illuminated regions, even when it has a lower reactivity. The model is used to simulate the grating formation process. This results in a calculated distribution of the monomer volume fractions as a function of position in polymer gratings. An excellent agreement with the nuclear microprobe measurements is obtained. ©2004 American Institute of Physics

Preparation of acid-responsive antibubbles from CaCO3-based Pickering emulsions.

HYPOTHESIS: Hydrophobized fumed silica particles were previously reported for producing antibubbles that are quite stable in neutral as well as in acidic media. To produce acid-responsive antibubbles (e.g., for gastric drug delivery), the silica nanoparticles must be replaced by suitable particles, e.g., calcium carbonate (CaCO 3), which can degrade at low pH to release the encapsulated drug. EXPERIMENTS: Two variants of CaCO 3-stabilized antibubbles were prepared (by using CaCO 3 particles pre-coated with stearic acid, or by using native CaCO 3 particles in combination with sodium stearoyl lactylate) and drug release was compared with classic antibubbles produced with hydrophobized fumed silica particles. FINDINGS: CaCO 3 particles (pre-coated with stearic acid) can be used to produce stable antibubbles, which provided an entrapment efficiency of a model drug (methylene blue, MB) of around 85%. A burst release of MB (∼60%) from the antibubbles was observed at pH 2 (i.e., the pH of the stomach), which was further increased to 80% during the next 30 min. On the contrary, at neutral pH, about 70% of the drug remained encapsulated for at least 2 h. We further demonstrated that the acidic conditions led to the desorption of CaCO 3 particles from the air-liquid interface resulting in the destabilization of the antibubbles and the release of drug-containing cores