Immobilization of Methyl Orange and Methylene Blue within the Matrix of Charge-Imbalanced Amphoteric Nanogels and Study of Dye Release Kinetics as a Function of Temperature and Ionic Strength

Cross-linked polyampholyte nanogels consisting of neutral N-isopropylacrylamide (NIPAM), negatively charged sodium salt of 2-acrylamido-2-methylpropanesulfonate (AMPS), and positively charged (3-acrylamidopropyltrimethylammonium chloride (APTAC) monomers were synthesized via conventional redox initiated free radical copolymerization using N,N-methylenebis(acrylamide) (MBAA) as a crosslinking agent. The resulting nanogels were characterized by means of FTIR and 1H NMR spectroscopy, dynamic light scattering (DLS) and zeta-potential measurements. Surface morphology was analyzed using scanning electron microscopy. Due to the presence of thermally responsive NIPAM units and varying molar ratios of anionic (AMPS) and cationic (APTAC) units, the resulting nanogels were responsive to multiple stimuli in aqueous media and can be used for controlled delivery of dyes. Thus, the NIPAM90-APTAC7.5-AMPS2.5 nanogel with an excess of the cationic units was chosen for immobilization of the anionic dye, methyl orange (MO), whereas the NIPAM90-APTAC2.5-AMPS7.5 nanogel with an excess of the anionic units was chosen for immobilization of the cationic dye, methylene blue (MB). The release kinetics of the dyes from the nanogel was studied depending on the phase transition temperature and the salt content. Mechanism of the dye release from the nanogel matrix was determined using the Ritger-Peppas equation. Disappearance of the ionic contacts between the charged groups of the nanogels and the ionic dyes was suggested to be the main reason for the diffusion of the dyes through the dialysis membrane into external solution.Peer reviewe

Synthesis and characterization of novel thermo- and salt-sensitive amphoteric terpolymers based on acrylamide derivatives

A novel linear amphoteric terpolymers based on neutral monomer - N-isopropylacrylamide (NIPAM), anionic monomer - 2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt (AMPS), and cationic monomer - (3-acrylamidopropyl) trimethylammonium chloride (APTAC) were synthesized by free-radical polymerization in aqueous solution and characterized by methods of H-1 NMR and FTIR spectroscopy, TGA, GPC, Dynamic light scattering (DLS) and zeta-potential. The thermal and salt sensitivity of amphoteric ternary polymers of various compositions, particularly, [NIPAM]:[AMPS]:[APTAC] = 90:2.5:7.5; 90:5:5; 90:7.5:2.5 mol.% were studied in aqueous and aqueous-salt solutions in the temperature range from 25 to 60 degrees C and at the NaCl ionic strength. interval from 10(-3) to 1M. It was found that due to hydrophobic/hydrophilic balance, the temperature dependent conformational and phase change of macromolecular chains becomes sensitive to salt addition and allows the fine-tuning of the phase transition. In aqueous and aqueous-salt solutions, the average hydrodynamic size of amphoteric terpolymers is varied from 8 to 300 nm exhibiting bimodal distribution at room temperature. The number average (M-n) and weight average (M-w) molecular weights, polydispersity index (PDI), and zeta-potentials of amphoteric terpolymers in aqueous solutions were determined.Peer reviewe

Conformational Parameters and Hydrodynamic Behavior of Poly(2-Methyl-2-Oxazoline) in a Broad Molar Mass Range

In this work, we report our results on the hydrodynamic behavior of poly(2-methyl-2-oxazoline) (PMeOx). PMeOx is gaining significant attention for use as hydrophilic polymer in pharmaceutical carriers as an alternative for the commonly used poly(ethylene glycol) (PEG), for which antibodies are found in a significant fraction of the human population. The main focus of the current study is to determine the hydrodynamic characteristics of PMeOx under physiological conditions, which serves as basis for better understanding of the use of PMeOx in pharmaceutical applications. This goal was achieved by studying PMeOx solutions in phosphate-buffered saline (PBS) as a solvent at 37 °C. This study was performed based on two series of PMeOx samples; one series is synthesized by conventional living cationic ring-opening polymerization, which is limited by the maximum chain length that can be achieved, and a second series is obtained by an alternative synthesis strategy based on acetylation of well-defined linear poly(ethylene imine) (PEI) prepared by controlled side-chain hydrolysis of a defined high molar mass of poly(2-ethyl-2-oxazoline). The combination of these two series of PMeOx allowed the determination of the Kuhn–Mark–Houwink–Sakurada equations in a broad molar mass range. For intrinsic viscosity, sedimentation and diffusion coefficients, the following expressions were obtained: η=0.015M0.77, s0=0.019M0.42 and D0=2600M−0.58, respectively. As a result, it can be concluded that the phosphate-buffered saline buffer at 37 °C represents a thermodynamically good solvent for PMeOx, based on the scaling indices of the equations. The conformational parameters for PMeOx chains were also determined, revealing an equilibrium rigidity or Kuhn segment length, (A) of 1.7 nm and a polymer chain diameter (d) of 0.4 nm. The obtained value for the equilibrium rigidity is very similar to the reported values for other hydrophilic polymers, such as PEG, poly(vinylpyrrolidone) and poly(2-ethyl-2-oxazoline), making PMeOx a relevant alternative to PEG

Isotope shift in the electron affinity of chlorine

The specific mass shift in the electron affinity between ^{35}Cl and ^{37}Cl has been determined by tunable laser photodetachment spectroscopy to be -0.51(14) GHz. The isotope shift was observed as a difference in the onset of the photodetachment process for the two isotopes. In addition, the electron affinity of Cl was found to be 29138.59(22) cm^{-1}, giving a factor of 2 improvement in the accuracy over earlier measurements. Many-body calculations including lowest-order correlation effects demonstrates the sensitivity of the specific mass shift and show that the inclusion of higher-order correlation effects would be necessary for a quantitative description.Comment: 16 pages, 6 figures, LaTeX2e, amsmat

Значение сердечного пептида NT-proBNP в оценке риска реваскуляризации миокарда у больных со сниженной фракцией изгнания левого желудочка

Objective: to substantiate a procedure for predicting the severity of postperfusion acute heart failure (AHF) from the baseline level of NT-proBNP during myocardial revascularization in patients with a left ventricular ejection fraction (LVEF) of less than 35%. Subjects and materials. Fifty-six patients with a LVEF of less than 35% were examined. A total of 3.5±0.1 (range 2—4) coronary arteries were shunted under cardio-pulmonary bypass (CPB) (71.0±5.5 min). The concentration of NT-proBNP was measured before surgery (Cardiac Reader®, Roche). Mortality rates, sympathomimetic agents’ dosages required after EC, and the frequency of use of intraaortic balloon pumping (IABP) were analyzed. Results. A good clinical course was observed in 47 cases (Group 1). AHF was recorded in 9 patients (Group 2). Comparative analysis demonstrated that the preoperative concentration of NT-proBNP (871±111 pg/ml in Group 1 and 1946±236 pg/ml in Group 2) was of the highest prognostic value as compared with the traditional indicators (p=0.0015). Patients with a NT-proBNP concentration of less than 600 pg/ml did not virtually need inotropic therapy after EC. In a group with a biomarker level of 600—1200 mg/ml, the infusion of dopamine and dobutamine achieved the traditional cardiotonic dosages and every three patients needed epinephrine. With NT-proBNP of 1200-2000 pg/ml, mortality from AHF was 15.4%; a need for epinephrine and IABC was 46.4 and 7.7%, respectively. The peptide concentration of more than 2000 pg/ml indicated the extremely high risk of severe AHF. In the postperfusion period, each patient was given epinephrine and an IABC system was installed in half of them. In this group mortality achieved 50%. Conclusion. It is expedient to determine a preoperative NT-proBNP concentration in a LVEF of less than 35% to predict AHF to be occurred after myocardial revascularization. The concentration of less than 1200 pg/ml may be considered to be a safe level of the peptide. Its content increase more than 2000 pg/ml suggests that there is an extremely high risk of severe AHF. The level of this biomarker may be a guide to choose an anesthetic tactic. Key words: NT-proBNP, cardiosurgery, heart failure.Цель исследования — обоснование методики прогнозирования тяжести постперфузионной острой сердечной недостаточности (ОСН) на основе исходного уровня NT-proBNP при реваскуляризации миокарда у больных с фракцией изгнания левого желудочка (ФИЛЖ) менее 35%. Материал и методы. Обследовали 56 больных с ФИЛЖ ниже 35%. Шунтировали 3,5±0,1 (2—4) коронарных артерии с искусственным кровообращением (ИК — 71,0±5,5 мин). Концентрацию NT-proBNP определяли перед операцией (Cardiac Reader®, Roche). Анализировали летальность, потребовавшиеся после ИК дозировки симпато-миметиков, частоту применения внутриаортальной баллонной контрпульсации (ВАБК). Результаты. Благополучное клиническое течение наблюдали в 47 случаях (группа 1). У 9 больных (группа 2) регистрировали ОСН. Наибольшую, в сравнении с традиционными показателями, прогностическую значимость (р=0,0015) при сравнительном анализе продемонстрировала предоперационная концентрация NT-proBNP (871±111 пг/мл в 1-й группе и 1946±236 пг/мл во 2-й группе). У больных с концентрацией NT-proBNP менее 600 пг/мл инотропная терапия после ИК практически не требовалась. В группе с уровнем биомаркёра 600-1200 пг/мл инфузия допамина и добутамина достигала традиционных «кардиотонических» дозировок, а у каждого третьего пациента был необходим адреналин. При NT-proBNP — 1200—2000 пг/мл, летальность от ОСН составила 15,4%, потребность в адреналине — 46,4%, ВАБК — 7,7%. Концентрация пептида более 2000 пг/мл указывала на крайне высокий риск развития тяжёлой ОСН. В постперфузионный период назначали адреналин каждому больному, а половине из них экстренно устанавливали систему для ВАБК. Летальность в этой группе достигла 50%. Заключение. Определение предоперационной концентрации NT-proBNP при ФИЛЖ менее 35% целесообразно для прогнозирования ОСН после реваскуляризации миокарда. «Безопасным» уровнем пептида можно считать концентрацию ниже 1200 пг/мл. Повышение его содержания более 2000 пг/мл свидетельствует о крайне высоком риске тяжёлой ОСН. Уровень данного биомаркера может быть ориентиром для выбора анестезиологической тактики. Ключевые слова: NT-proBNP, кардиохирургия, сердечная недостаточность