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1. STUDY OF THE EFFECT OF PROPYLENE GLYCOL ON THE PROPERTIES OF POLOXAMER 338 SOLUTIONS.

Author

Liapunov, Oleksii, Bezugla, Olena, Lyapunov, Nikolay, and Lysokobylka, Oleksii

Subjects
PROPYLENE glycols, POLOXAMERS, ELECTRON paramagnetic resonance, VISCOSITY, MICELLES
Abstract

The aim. Study of the characteristics of 20 % solutions of poloxamer 338 (P338) in water and mixed solvents water - propylene glycol (PG) at various temperatures using rotational viscometry and the spin probe method. Materials and methods. 20 % m/m solutions of P338 in water and water - PG mixtures were the objects of re- search. The solutions were studied by rotational viscometry at 25 °C, 32 °C i 37 °C; the flow behaviour, low-yield stress (τ0), hysteresis area (SN) and dynamic or apparent viscosity (η) were determined. Spin probes based on fatty acids, which differ in molecular structure, solubility, and radical localisation, were added to the solutions. Electron paramagnetic resonance (EPR) spectra was obtained to determine their type and parameters. Results. Depending on the content, PG affects the rheological properties of 20 % P338 solution. The ability of this solution to undergo thermally induced sol-gel transitions, resulting in the formation of gels with plastic flow behaviour at temperatures of 32 °C and 37 °C, is maintained at PG content of up to 20 %. At 37 °C and a 30 % PG content, an atypical thixotropic gel is formed. The rheological characteristics of gels containing 10-20 % PG at 32 °C and 37 °C are higher than those of gels without PG. The increase in the PG concentration from 0 to 40 % generally has little effect on the rotational correlation times (T) and values of the order parameter (S) of the spin probes. In the case of the ammonium salt of 5-doxylstearic acid (5-DSA NH4 salt), the anisotropic EPR spectra at a PG concentration of 40 % undergoes a transformation, becoming a triplet. This coincides with the loss of the ability of 20 % P338 solutions to thermally induced sol↔gel transitions. An increase in the concentration of PG (in contrast to ethanol) does not lead to the solvation of P338 micelle cores by the dispersion medium. The transformation of the EPR spectrum of the 5-DSA NH4 salt into a triplet is probably the result of the interaction between PG and the hydrophilic shell of micelles through the formation of hydrogen bonds. Conclusions. The rheological properties of 20 % P338 solution are affected by the PG, depending on its content. The P338 solutions can undergo a thermally induced sol↔gel transition, provided that the PG content does not exceed 30 %. A correlation has been identified between alterations in the rheological properties of 20 % P338 solution and the corresponding change in the types of EPR spectra observedfor the 5-DSA NH4 salt, namely a transition from anisotropic spectra to triplet. As the PG content in the P338 solution increases up to 40 %, the solvation of micelle cores by the dispersion medium does not occur. It may be posited that the alteration in the structure of P338 micelles is a consequence of the interaction between PG and their hydrophilic shell [ABSTRACT FROM AUTHOR] more...

Published
2024
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2. STUDY OF THE EFFECT OF ETHANOL ON THE PROPERTIES OF POLOXAMER 338 SOLUTIONS BY ROTATIONAL VISCOMETRY AND SPIN PROBE METHOD.

Author

Liapunov, Oleksii, Bezugla, Olena, Liapunova, Anna, and Lysokobylka, Oleksii

Subjects
ETHANOL, POLOXAMERS, VISCOMETRY, SOLUTION (Chemistry), MOLECULAR structure
Abstract

The aim. Study the properties of 20 % solutions of poloxamer 338 (P338) in water and mixed solvents water-ethanol using rotational viscometry and the spin probe method at various temperatures. Materials and methods. 20 % m/m solutions of P338 in water and water -- ethanol mixtures were the objects of research. The solutions were studied by rotational viscometry at various temperatures; the flow behaviour, lower yield stress (τ0) and dynamic or apparent viscosity (η) were determined. Spin probes based on fatty acids, which differ in molecular structure, solubility, and radical localization, were added to the solutions. Electron paramagnetic resonance (EPR) spectra were obtained to determine their type and parameters. Results. Depending on the content, ethanol affects the rheological properties of 20 % solution of P338. The solution was demonstrated to be able to thermally induce sol→gel transition at 32 °C when ethanol content is 5 % m/m. The rheological parameters of the gel at 32 °C and 37 °C exhibit an increase (in comparison to the gel without ethanol), accompanied by a reduction in the packing density of polypropylene oxide (PPO) chains within the cores of P338 micelles. At an ethanol content of 10 % m/m, the gel formation temperature rises to 40 °C. At ethanol content of 15 % m/m and above, 20 % P338 solutions do not form gels at temperatures between 25 °C and 40 °C. The values of rotational correlation times (τ) and the order parameter (S) of fatty acid-based spin probes were observed to decrease with increasing ethanol content up to 30 % m/m; in the case of the ammonium salt of 5-doxylstearic acid (5-DSA NH4 salt), the anisotropic EPR spectra transform, becoming a superposition of two triplets and subsequently a triplet. P338 solutions retain their ability to undergo thermally induced sol↔gel transitions as long as the EPR spectra of this probe exhibit anisotropy at temperatures ranging from 25 °C to 37 °C. As the concentration of ethanol in the solution increases, the solvation of the cores of P338 micelles by the dispersion medium of the solution also increases. Conclusions. It was demonstrated that ethanol, when added to the 20 % P338 solution, results in changes to the rheological properties of this solution. However, at the ethanol content of 5-10 % m/m, the ability of P338 to thermally induced sol→gel transition remains unaltered. The rheological properties of the 20 % P338 solution exhibit a correlation with the observed change in EPR spectra types for the 5-DSA NH4 salt. As the ethanol content in the solution increases, the solvation of P338 micelle cores by the dispersion medium increases, accompanied by decreased density and orderliness of the PPO chains packing in the micelle cores [ABSTRACT FROM AUTHOR] more...

Published
2024
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3. INTERACTION OF SURFACTANTS WITH POLOXAMERS 338 AND ITS EFFECT ON SOME PROPERTIES OF CREAM BASE.

Author

Bezuglaya, Elena, Lyapunov, Nikolay, Lysokobylka, Oleksii, Liapunov, Oleksii, Klochkov, Vladimir, Grygorova, Ganna, and Liapunova, Anna

Subjects
OINTMENTS, SURFACE active agents, POLOXAMERS, BASES (Chemistry), HYDRODYNAMICS, MICELLES, ABSORPTION, ADHESIVES
Abstract

Copyright of ScienceRise: Pharmaceutical Science is the property of PC TECHNOLOGY CENTER and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...

Published
2021
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4. Interaction of surfactants with poloxamers 338 and its effect on some properties of cream base

Author

Elena Bezuglaya, Nikolay Lyapunov, Oleksii Lysokobylka, Oleksii Liapunov, Volodimir Klochkov, Hanna Grygorova, and Anna Liapunova

Subjects
RS1-441, Pharmacy and materia medica, surfactant, micelle, spin probe, rotational correlation time (τ), rheological parameters, poloxamer 338 (p338), cream base, General Pharmacology, Toxicology and Pharmaceutics
Abstract

The aim.Study of the interaction of surfactants with poloxamer 338 (P338) and the effect of P338 on the properties of cream bases. Materials and methods. Solutions of the surfactants and P338 as well as cream bases were under study. The average hydrodynamic diameter (Dh) and zeta potential (ζ‑potential) were determined by the light scattering intensity and electrophoretic mobility of micelles. The electron paramagnetic resonance (EPR) spectra of spin probes in micelles, solvents and bases were obtained; the type of spectrum, isotropic constant (AN), rotational correlation times (τ) and anisotropy parameter (ε) were determined. Liquids and cream bases were studied by capillary and rotational viscometry; the flow behaviour and yield stress (t0), dynamic and apparent viscosity (η) as well as the hysteresis (thixotropic) area (AH) were determined. The microstructure of the bases was examined by optical microscopy. The strength of adhesion (Sm) was assessed by the pull-off test, and the absorption of water was studied by dialysis. Results.Under the impact of P338 the hydrodynamic diameters of micelles formed by cationic, anionic and nonionic surfactants decreased as well as the absolute values of their ζ‑potential became lower, but the microviscosity of the micelle nuclei increased. There was also a change in the structure of the aggregates of surfactant with fatty alcohols; EPR spectra, which were superpositions characteristic for the lateral phase separation, converted into triplets that indicated the uniform distribution of lipophilic probes in the surfactant phase. When the content of P338 increased to 17 %, the rheological parameters of the bases increased drastically, the flow behaviour and the microstructure changed. The bases had the consistency of cream within temperature range from 25 °C to 70 °C and completely restored their apparent viscosity, which had decreased under shear stress. P338 enhances the adhesive properties of the bases. Due to their microstructure, cream bases have a lower ability to absorb water compared to a solution and gel containing 17 % and 20 % P338, respectively. Conclusions.The structure of surfactant micelles and aggregates of surfactants with fatty alcohols changed under impact of P338 due to the interaction of surfactants with P338. As a result of this interaction, at a sufficiently high concentration of P338, the microstructure and flow behaviour of bases changed, their rheological parameters, which remain high at temperatures from 25 °C to 70 °C, increased significantly, and water absorption parameters decreased. The bases with P338 were more adhesive more...

Published
2021

5. Взаимодействие поверхностно-активных веществ с полоксамером 338 и его влияние на некоторые свойства кремовых основ

Subjects
спіновий зонд, surfactant, мицелла, rotational correlation time (τ), rheological parameters, полоксамер 338 (Р338), час кореляції обертальної дифузії (τ), ПАВ, реопараметри, кремова основа, время корреляции вращательной диффузии (τ), спиновый зонд, ПАР, кремовая основа, micelle, spin probe, cream base, poloxamer 338 (P338), реопараметры, міцела
Abstract

The aim. Study of the interaction of surfactants with poloxamer 338 (P338) and the effect of P338 on the properties of cream bases. Materials and methods. Solutions of the surfactants and P338 as well as cream bases were under study. The average hydrodynamic diameter (Dh) and zeta potential (ζ‑potential) were determined by the light scattering intensity and electrophoretic mobility of micelles. The electron paramagnetic resonance (EPR) spectra of spin probes in micelles, solvents and bases were obtained; the type of spectrum, isotropic constant (AN), rotational correlation times (τ) and anisotropy parameter (ε) were determined. Liquids and cream bases were studied by capillary and rotational viscometry; the flow behaviour and yield stress (t0), dynamic and apparent viscosity (η) as well as the hysteresis (thixotropic) area (AH) were determined. The microstructure of the bases was examined by optical microscopy. The strength of adhesion (Sm) was assessed by the pull-off test, and the absorption of water was studied by dialysis. Results. Under the impact of P338 the hydrodynamic diameters of micelles formed by cationic, anionic and nonionic surfactants decreased as well as the absolute values of their ζ‑potential became lower, but the microviscosity of the micelle nuclei increased. There was also a change in the structure of the aggregates of surfactant with fatty alcohols; EPR spectra, which were superpositions characteristic for the lateral phase separation, converted into triplets that indicated the uniform distribution of lipophilic probes in the surfactant phase. When the content of P338 increased to 17 %, the rheological parameters of the bases increased drastically, the flow behaviour and the microstructure changed. The bases had the consistency of cream within temperature range from 25 °C to 70 °C and completely restored their apparent viscosity, which had decreased under shear stress. P338 enhances the adhesive properties of the bases. Due to their microstructure, cream bases have a lower ability to absorb water compared to a solution and gel containing 17 % and 20 % P338, respectively. Conclusions. The structure of surfactant micelles and aggregates of surfactants with fatty alcohols changed under impact of P338 due to the interaction of surfactants with P338. As a result of this interaction, at a sufficiently high concentration of P338, the microstructure and flow behaviour of bases changed, their rheological parameters, which remain high at temperatures from 25 °C to 70 °C, increased significantly, and water absorption parameters decreased. The bases with P338 were more adhesive, Цель. Исследовать взаимодействие между поверхностно-активными веществами (ПАВ) и полоксамером 338 (Р338) и влияние Р338 на свойства кремовых основ. Материалы и методы. Исследовали растворы ПАВ и Р338, а также кремовые основы. По интенсивности рассеяния света и электрофоретической подвижности мицелл определяли их средний гидродинамический диаметр (Dh) и ζ-потенциал. Получали спектры электронного парамагнитного резонанса (ЭПР) спиновых зондов в мицеллах, растворителях и основах; определяли тип спектра, изотропную константу (AN), времена корреляции вращательной диффузии (τ), параметр анизотропии (ε). Жидкости и основы исследовали методами капиллярной и ротационной вискозиметрии; определяли тип течения и нижний предел текучести (t0), динамическую и кажущуюся вязкость (η), площадь петли гистерезиса (AH). Микроструктуру основ исследовали методом оптической микроскопии. Cилу адгезии (Sm) определяли методом прямого отрыва, а абсорбцию воды – методом диализа. Результаты. Под влиянием Р338 уменьшаются гидродинамические диаметры мицелл катионного, анионного и неионного ПАВ, снижаются абсолютные величины их ζ-потенциалов и повышается микровязкость ядер мицелл. Происходит также изменение структуры агрегатов ПАВ с жирными спиртами; спектры ЭПР из суперпозиций, характерных для латерального разделения фаз, превращаются в триплеты, свидетельствующие о равномерном распределении липофильных зондов в фазе ПАВ. При повышении содержания Р338 до 17 % резко возрастают реологические параметры основ, изменяется тип их течения и микроструктура. Основы имели характерную для кремов консистенцию в диапазоне температур от 25°С до 70°С и полностью восстанавливали кажущуюся вязкость, которая уменьшилась при приложении напряжения сдвига. P338 усиливает адгезивные свойства кремовых основ. Из-за микроструктуры кремовых основ им свойственна меньшая способность к абсорбции воды по сравнению с раствором и гелем, содержащим соответственно 17 % и 20 % Р338. Выводы. Структура мицелл ПАВ и агрегатов ПАВ с жирными спиртами изменяется под воздействием Р338, что обусловлено взаимодействием ПАВ и Р338. Вследствие этого взаимодействия при достаточно высокой концентрации Р338 изменяются микроструктура и тип течения основ, существенно возрастают их реологические параметры, которые остаются высокими при температурах от 25 °С до 70 °С, и снижаются параметры абсорбции воды. Основы с P338 более адгезивны, Мета. Дослідити взаємодію поверхнево-активниx речовин (ПАР) з полоксамером 338 (Р338) та вплив Р338 на властивості кремових основ. Матеріали та методи. Досліджували розчини ПАР і Р338, а також кремові основи. За інтенсивністю розсіювання світла та електрофоретичною рухливістю міцел визначали їх середній гідродинамічний діаметр (Dh) та ζ‑потенціал. Отримували спектри електронного парамагнітного резонансу (ЕПР) спінових зондів у міцелах, розчинниках і основах; визначали тип спектра, ізотропну константу (АN), часи кореляції обертальної дифузії (τ), параметр анізотропії (ε). Рідини й кремові основи досліджували методами капілярної та ротаційної віскозиметрії; визначали тип течії та нижню межу плинності (t0), динамічну та уявну в’язкість (η), площу петлі гістерезису (AH). Мікроструктуру основ досліджували методом оптичної мікроскопії. Cилу адгезії (Sm) визначали методом прямого відриву, а абсорбцію води – методом діалізу. Результати. Під впливом Р338 зменшуються гідродинамічні діаметри міцел катіонної, аніонної та неіонної ПАР, знижуються абсолютні величини їх ζ‑потенціалів і підвищується мікров’язкість ядер міцел. Відбувається також зміна структури агрегатів ПАР з жирними спиртами; спектри ЕПР з суперпозицій, характерних для латерального розділу фаз, перетворюються на триплети, що свідчать про рівномірний розподіл ліпофільних зондів у фазі ПАР. При підвищенні вмісту Р338 до 17 % суттєво зростають реологічні параметри основ, змінюється тип їх течії та мікроструктура. Основи мали характерну для кремів консистенцію в діапазоні температур від 25 °С до 70°С та повністю відновлювали уявну в’язкість, що зменшувалася під напругою зсуву. P338 посилює адгезивні властивості кремових основ. Через мікроструктуру кремових основ їм властива менша здатність до абсорбції води порівняно з розчином і гелем, що містять відповідно 17 % і 20 % Р338. Висновки. Структура міцел ПАР і агрегатів ПАР з жирними спиртами змінюється під впливом Р338, що обумовлено взаємодією ПАР і Р338. Внаслідок цієї взаємодії при достатньо високій концентрації Р338 змінюються мікроструктура та тип течії основ, суттєво зростають їх реологічні параметри, що залишаються високими при температурах від 25 °С до 70 °С, і знижуються параметри абсорбції води. Основи з P338 є більш адгезивними more...

Published
2021

7. Uncoupling of increased cellular oxidative stress and myocardial ischemia reperfusion injury by directed sarcolemma stabilization.

Author

Martindale, Joshua J. and Metzger, Joseph M.

Subjects
*OXIDATIVE stress, *CORONARY disease, *REPERFUSION injury, *SARCOLEMMA, *CELL death, HEART dissection
Abstract

Abstract: Myocardial ischemia/reperfusion (I/R) injury is a major clinical problem leading to cardiac dysfunction and myocyte death. It is widely held that I/R causes damage to membrane phospholipids, and is a significant mechanism of cardiac I/R injury. Molecular dissection of sarcolemmal damage in I/R, however, has been difficult to address experimentally. We studied here cardiac I/R injury under conditions targeting gain- or loss-of sarcolemma integrity. To implement gain-in-sarcolemma integrity during I/R, synthetic copolymer-based sarcolemmal stabilizers (CSS), including Poloxamer 188 (P188), were used as a tool to directly stabilize the sarcolemma. Consistent with the hypothesis of sarcolemmal stabilization, cellular markers of necrosis and apoptosis evident in untreated myocytes were fully blocked in sarcolemma stabilized myocytes. Unexpectedly, sarcolemmal stabilization of adult cardiac myocytes did not affect the status of myocyte-generated oxidants or lipid peroxidation in two independent assays. We also investigated the loss of sarcolemmal integrity using two independent genetic mouse models, dystrophin-deficient mdx or dysferlin knockout (Dysf KO) mice. Both models of sarcolemmal loss-of-function were severely affected by I/R injury ex vivo, and this was lessened by CSS. In vivo studies also showed that infarct size was significantly reduced in CSS-treated hearts. Mechanistically, these findings support a model whereby I/R-mediated increased myocyte oxidative stress is uncoupled from myocyte injury. Because the sarcolemma stabilizers used here do not transit across the myocyte membrane this is evidence that intracellular targets of oxidants are not sufficiently altered to affect cell death when sarcolemma integrity is preserved by synthetic stabilizers. These findings, in turn, suggest that sarcolemma destabilization, and consequent Ca2+ mishandling, as a focal initiating mechanism underlying myocardial I/R injury. [Copyright &y& Elsevier] more...

Published
2014
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