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Solid-in-Oil-in-Water Emulsion: An Innovative Paradigm to Improve Drug Stability and Biological Activity.
Sawant, A, Kamath, S, Kg, H, Kulyadi, GP
AAPS PharmSciTech. 2021;(5):199
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Abstract
An emulsion is a biphasic dosage form comprising of dispersed phase containing droplets that are uniformly distributed into a surrounding liquid which forms the continuous phase. An emulsifier is added at the interface of two immiscible liquids to stabilize the thermodynamically unstable emulsion. Various types of emulsions such as water-in-oil (w-o), oil-in-water (o-w), microemulsions, and multiple emulsions are used for delivering certain drugs in the body. Water (aqueous) phase is commonly used for encapsulating proteins and several other drugs in water-in-oil-in-water (w-o-w) emulsion technique. But this method has posed certain problems such as decreased stability, burst release, and low entrapment efficiency. Thus, a novel "solid-in-oil-in-water" (s-o-w) emulsion system was developed for formulating certain drugs, probiotics, proteins, antibodies, and tannins to overcome these issues. In this method, the active ingredient is encapsulated as a solid and added to an oil phase, which formed a solid-oil dispersion. This dispersion was then mixed with water to form a continuous phase for enhancing the drug absorption. This article focuses on the various studies done to investigate the effectiveness of formulations prepared as solid-oil-water emulsions in comparison to conventional water-oil-water emulsions. A summary of the results obtained in each study is presented in this article. The s-o-w emulsion technique may become beneficial in near future as it has shown to improve the stability and efficacy of the entrapped active ingredient.
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Foliar water and solute absorption: an update.
Fernández, V, Gil-Pelegrín, E, Eichert, T
The Plant journal : for cell and molecular biology. 2021;(4):870-883
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Abstract
The absorption of water and solutes by plant leaves has been recognised since more than two centuries. Given the polar nature of water and solutes, the mechanisms of foliar uptake have been proposed to be similar for water and electrolytes, including nutrient solutions. Research efforts since the 19th century focussed on characterising the properties of cuticles and applying foliar sprays to crop plants as a tool for improving crop nutrition. This was accompanied by the development of hundreds of studies aimed at characterising the chemical and structural nature of plant cuticles from different species and the mechanisms of cuticular and, to a lower extent, stomatal penetration of water and solutes. The processes involved are complex and will be affected by multiple environmental, physico-chemical and physiological factors which are only partially clear to date. During the last decades, the body of evidence that water transport across leaf surfaces of native species may contribute to water balances (absorption and loss) at an ecosystem level has grown. Given the potential importance of foliar water absorption for many plant species and ecosystems as shown in recent studies, the aim of this review is to first integrate current knowledge on plant surface composition, structure, wettability and physico-chemical interactions with surface-deposited matter. The different mechanisms of foliar absorption of water and electrolytes and experimental procedures for tracing the uptake process are discussed before posing several outstanding questions which should be tackled in future studies.
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Application of Monolayer Graphene and Its Derivative in Cryo-EM Sample Preparation.
Wu, K, Wu, D, Zhu, L, Wu, Y
International journal of molecular sciences. 2021;(16)
Abstract
Cryo-electron microscopy (Cryo-EM) has become a routine technology for resolving the structure of biological macromolecules due to the resolution revolution in recent years. The specimens are typically prepared in a very thin layer of vitrified ice suspending in the holes of the perforated amorphous carbon film. However, the samples prepared by directly applying to the conventional support membranes may suffer from partial or complete denaturation caused by sticking to the air-water interface (AWI). With the application in materials, graphene has also been used recently to improve frozen sample preparation instead of a suspended conventional amorphous thin carbon. It has been proven that graphene or graphene oxide and various chemical modifications on its surface can effectively prevent particles from adsorbing to the AWI, which improves the dispersion, adsorbed number, and orientation preference of frozen particles in the ice layer. Their excellent properties and thinner thickness can significantly reduce the background noise, allowing high-resolution three-dimensional reconstructions using a minimum data set.
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Hormonal and environmental signaling pathways target membrane water transport.
Maurel, C, Tournaire-Roux, C, Verdoucq, L, Santoni, V
Plant physiology. 2021;(4):2056-2070
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Plant water transport and its molecular components including aquaporins are responsive, across diverse time scales, to an extremely wide array of environmental and hormonal signals. These include water deficit and abscisic acid (ABA) but also more recently identified stimuli such as peptide hormones or bacterial elicitors. The present review makes an inventory of corresponding signalling pathways. It identifies some main principles, such as the central signalling role of ROS, with a dual function of aquaporins in water and hydrogen peroxide transport, the importance of aquaporin phosphorylation that is targeted by multiple classes of protein kinases, and the emerging role of lipid signalling. More studies including systems biology approaches are now needed to comprehend how plant water transport can be adjusted in response to combined stresses.
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Fungal Guttation, a Source of Bioactive Compounds, and Its Ecological Role-A Review.
Krain, A, Siupka, P
Biomolecules. 2021;(9)
Abstract
Guttation is a common phenomenon in the fungal kingdom. Its occurrence and intensity depend largely on culture conditions, such as growth medium composition or incubation temperature. As filamentous fungi are a rich source of compounds, possessing various biological activities, guttation exudates could also contain bioactive substances. Among such molecules, researchers have already found numerous mycotoxins, antimicrobials, insecticides, bioherbicides, antiviral, and anticancer agents in exudate droplets. They belong to either secondary metabolites (SMs) or proteins and are secreted with different intensities. The background of guttation, in terms of its biological role, in vivo, and promoting factors, has been explored only partially. In this review, we describe the metabolites present in fungal exudates, their diversity, and bioactivities. Pointing to the significance of fungal ecology and natural products discovery, selected aspects of guttation in the fungi are discussed.
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The mutual interactions of RNA, counterions and water - quantifying the electrostatics at the phosphate-water interface.
Fingerhut, BP
Chemical communications (Cambridge, England). 2021;(96):12880-12897
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Abstract
The structure and dynamics of polyanionic biomolecules, like RNA, are decisively determined by their electric interactions with the water molecules and the counterions in the environment. The solvation dynamics of the biomolecules involves a subtle balance of non-covalent and many-body interactions with structural fluctuations due to thermal motion occurring in a femto- to subnanosecond time range. This complex fluctuating many particle scenario is crucial in defining the properties of biological interfaces with far reaching significance for the folding of RNA structures and for facilitating RNA-protein interactions. Given the inherent complexity, suited model systems, carefully calibrated and benchmarked by experiments, are required to quantify the relevant interactions of RNA with the aqueous environment. In this feature article we summarize our recent progress in the understanding of the electrostatics at the biological interface of double stranded RNA (dsRNA) and transfer RNA (tRNA). Dimethyl phosphate (DMP) is introduced as a viable and rigorously accessible model system allowing the interaction strength with water molecules and counterions, their relevant fluctuation timescales and the spatial reach of interactions to be established. We find strong (up to ≈90 MV cm-1) interfacial electric fields with fluctuations extending up to ≈20 THz and demonstrate how the asymmetric stretching vibration νAS(PO2)- of the polarizable phosphate group can serve as the most sensitive probe for interfacial interactions, establishing a rigorous link between simulations and experiment. The approach allows for the direct interfacial observation of interactions of biologically relevant Mg2+ counterions with phosphate groups in contact pair geometries via the rise of a new absorption band imposed by exchange repulsion interactions at short interatomic distances. The systematic extension to RNA provides microscopic insights into the changes of the hydration structure that accompany the temperature induced melting of the dsRNA double helix and quantify the ionic interactions in the folded tRNA. The results show that pairs of negatively charged phosphate groups and Mg2+ ions represent a key structural feature of RNA embedded in water. They highlight the importance of binding motifs made of contact pairs in the electrostatic stabilization of RNA structures that have a strong impact on the surface potential and enable the fine tuning of the local electrostatic properties which are expected to be relevant for mediating the interactions between biomolecules.
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[Solid State NMR Investigation for Molecular States of Specialized Formulation to Improve the Water Solubility of Poorly Water-soluble Drugs].
Higashi, K
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 2021;(9):1063-1069
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Abstract
70-90% of recently developed new drug candidates are poorly soluble in water, which creates a series of thorny challenges in developing its oral dosage forms, resulting in low bioavailability. In pre-formulation study, various specialized formulations have been developed to improve drug solubility. Intermolecular interactions between drug and excipients in the formulations can modify the drug state and achieve the improvement of drug solubility. Therefore, the understanding of intermolecular interaction is essential to design formulations with higher quality and to assure the quality as a pharmaceutical product. Solid-state NMR has attracted much attention as a promising method to evaluate the molecular state of a drug and the interaction between a drug and excipient in its formulation. I have applied solid-state NMR and its characteristic technique, namely magic-angle spinning (MAS), for various specialized formulations including amorphous solid dispersion, supersaturated solution, drug-loaded organic nanotube, and drug nanosuspension. The intermolecular interactions of drug and excipient in amorphous solid dispersion have been identified by 13C and 15N solid-state NMR. High-resolution MAS determined the interaction modes of drug and excipient in a supersaturated solution. The two-step dissolution profile of drug from organic nanotube was understood, based on the molecular states revealed by the combination of various solid-state NMR techniques. A suspended-state NMR clarified the nanostructure of drug nanoparticles dispersed in water. It is expected that more qualified pharmaceutical formulations with improved drug solubility can be designed based on the remarkable development of recent solid-state NMR technology.
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Shining New Light on the Kinetics of Water Uptake by Organic Aerosol Particles.
Diveky, ME, Gleichweit, MJ, Roy, S, Signorell, R
The journal of physical chemistry. A. 2021;(17):3528-3548
Abstract
The uptake of water vapor by various organic aerosols is important in a number of applications ranging from medical delivery of pharmaceutical aerosols to cloud formation in the atmosphere. The coefficient that describes the probability that the impinging gas-phase molecule sticks to the surface of interest is called the mass accommodation coefficient, αM. Despite the importance of this coefficient for the description of water uptake kinetics, accurate values are still lacking for many systems. In this Feature Article, we present various experimental techniques that have been evoked in the literature to study the interfacial transport of water and discuss the corresponding strengths and limitations. This includes our recently developed technique called photothermal single-particle spectroscopy (PSPS). The PSPS technique allows for a retrieval of αM values from three independent, yet simultaneous measurements operating close to equilibrium, providing a robust assessment of interfacial mass transport. We review the currently available data for αM for water on various organics and discuss the few studies that address the temperature and relative humidity dependence of αM for water on organics. The knowledge of the latter, for example, is crucial to assess the water uptake kinetics of organic aerosols in the Earth's atmosphere. Finally, we argue that PSPS might also be a viable method to better restrict the αM value for water on liquid water.
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Emerging consensus on the collapse of unfolded and intrinsically disordered proteins in water.
Best, RB
Current opinion in structural biology. 2020;:27-38
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Abstract
Establishing the degree of collapse of unfolded or disordered proteins is a fundamental problem in biophysics, because of its relation to protein folding and to the function of intrinsically disordered proteins. However, until recently, different experiments gave qualitatively different results on collapse and there were large discrepancies between experiments and all-atom simulations. New methodology introduced in the past three years has helped to resolve the differences between experiments, and improvements in simulations have closed the gap between experiment and simulation. These advances have led to an emerging consensus on the collapse of disordered proteins in water.
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Ozonation as a Method of Abiotic Elicitation Improving the Health-Promoting Properties of Plant Products-A Review.
Sachadyn-Król, M, Agriopoulou, S
Molecules (Basel, Switzerland). 2020;(10)
Abstract
In this review, the primary objective was to systematize knowledge about the possibility of improving the health-promoting properties of raw plant products, defined as an increase in the content of bioactive compounds, by using ozone. The greatest attention has been paid to the postharvest treatment of plant raw materials with ozone because of its widespread use. The effect of this treatment on the health-promoting properties depends on the following different factors: type and variety of the fruit or vegetable, form and method of ozone treatment, and dosage of ozone. It seems that ozone applied in the form of ozonated water works more gently than in gaseous form. Relatively high concentration and long contact time used simultaneously might result in increased oxidative stress which leads to the degradation of quality. The majority of the literature demonstrates the degradation of vitamin C and deterioration of color after treatment with ozone. Unfortunately, it is not clear if ozone can be used as an elicitor to improve the quality of the raw material. Most sources prove that the best results in increasing the content of bioactive components can be obtained by applying ozone at a relatively low concentration for a short time immediately after harvest.