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Angewandte Chemie (International Ed. in... Apr 2022Responsive fluorescent materials offer a high potential for sensing and (bio-)imaging applications. To investigate new concepts for such materials and to broaden their...
Responsive fluorescent materials offer a high potential for sensing and (bio-)imaging applications. To investigate new concepts for such materials and to broaden their applicability, the previously reported non-fluorescent zinc(II) complex [Zn(L)] that shows coordination-induced turn-on emission was encapsulated into a family of non-fluorescent polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) diblock copolymer micelles leading to brightly emissive materials. Coordination-induced turn-on emission upon incorporation and ligation of the [Zn(L)] in the P4VP core outperform parent [Zn(L)] in pyridine solution with respect to lifetimes, quantum yields, and temperature resistance. The quantum yield can be easily tuned by tailoring the selectivity of the employed solvent or solvent mixture and, thus, the tendency of the PS-b-P4VP diblock copolymers to self-assemble into micelles. A medium-dependent off-on sensor upon micelle formation could be established by suppression of non-micelle-borne emission background pertinent to chloroform through controlled acidification indicating an additional pH-dependent process.
Topics: Micelles; Polymers; Solvents
PubMed: 35129881
DOI: 10.1002/anie.202117570 -
The EMBO Journal Jun 2021Paraspeckles are constructed by NEAT1_2 architectural long noncoding RNAs. Their characteristic cylindrical shapes, with highly ordered internal organization,...
Paraspeckles are constructed by NEAT1_2 architectural long noncoding RNAs. Their characteristic cylindrical shapes, with highly ordered internal organization, distinguish them from typical liquid-liquid phase-separated condensates. We experimentally and theoretically investigated how the shape and organization of paraspeckles are determined. We identified the NEAT1_2 RNA domains responsible for shell localization of the NEAT1_2 ends, which determine the characteristic internal organization. Using the soft matter physics, we then applied a theoretical framework to understand the principles that determine NEAT1_2 organization as well as shape, number, and size of paraspeckles. By treating paraspeckles as amphipathic block copolymer micelles, we could explain and predict the experimentally observed behaviors of paraspeckles upon NEAT1_2 domain deletions or transcriptional modulation. Thus, we propose that paraspeckles are block copolymer micelles assembled through a type of microphase separation, micellization. This work provides an experiment-based theoretical framework for the concept that ribonucleoprotein complexes (RNPs) can act as block copolymers to form RNA-scaffolding biomolecular condensates with optimal sizes and structures in cells.
Topics: Cell Line; Humans; Micelles; Polymers; RNA, Long Noncoding; Ribonucleoproteins
PubMed: 33885174
DOI: 10.15252/embj.2020107270 -
FEBS Letters Aug 2022Casein micelles are extracellular polydisperse assemblies of unstructured casein proteins. Caseins are the major component of milk. Within casein micelles, casein... (Review)
Review
Casein micelles are extracellular polydisperse assemblies of unstructured casein proteins. Caseins are the major component of milk. Within casein micelles, casein molecules are stabilised by binding to calcium phosphate nanoclusters and, by acting as molecular chaperones, through multivalent interactions. In the light of such interactions, we discuss whether casein micelles can be considered as extracellular condensates formed by liquid-liquid phase separation. We analyse the sequence, structure and interactions of caseins in comparison with proteins forming intracellular condensates. Furthermore, we review the similarities between caseins and small heat-shock proteins whose chaperone activity is linked to phase separation of proteins. By bringing these observations together, we describe a regulatory mechanism for protein condensates, as exemplified by casein micelles.
Topics: Animals; Caseins; Intrinsically Disordered Proteins; Micelles; Milk; Molecular Chaperones; Protein Folding
PubMed: 35815989
DOI: 10.1002/1873-3468.14449 -
Current Pharmaceutical Design 2021Surfactants are amphiphilic molecules of great interest in the pharmaceutical field which are used in combination with other adjuvants to solubilize poorly soluble... (Review)
Review
Surfactants are amphiphilic molecules of great interest in the pharmaceutical field which are used in combination with other adjuvants to solubilize poorly soluble drugs, improve their dissolution profile, promote permeation, improve drug delivery, enhance stabilization, among other characteristics. Literature shows that surfactants are included in several pharmaceutical compositions: tablets, solid dispersions, emulsions, microemulsions, nanoemulsions, liposomes and niosomes. This review aims to elucidate the different classes of surfactants based on their charges (cationic, anionic, nonionic, zwitterionic, and dimeric), the micelles formation process, and how surfactant molecules geometry can affect this phenomenon. Moreover, current studies regarding the benefits of surfactants in the development of formulations are presented. Finally, a discussion on how charges and chain length of surfactants can affect the stratum corneum epithelial cells leading to increased permeation or skin irritability is reported.
Topics: Drug Delivery Systems; Emulsions; Humans; Micelles; Skin Absorption; Surface-Active Agents
PubMed: 34042031
DOI: 10.2174/1381612827666210526091825 -
Journal of Colloid and Interface Science Sep 2021There is an increased interest in the use of natural surfactant as replacements for synthetic surfactants due to their biosustainable and biocompatible properties. A...
UNLABELLED
There is an increased interest in the use of natural surfactant as replacements for synthetic surfactants due to their biosustainable and biocompatible properties. A category of natural surfactants which are attracting much current interest is the triterpenoid saponins; surface active components found extensively in a wide range of plant species. A wide range of different saponin structures exist, depending upon the plant species they are extracted from; but regardless of the variation in structural details they are all highly surface active glycosides. Greater exploitation and application requires a characterisation and understanding of their basic adsorption and self-assembly properties.
HYPOTHESIS
Glycyrrhizic acid, extracted from Licorice root, is a monodesmosidic triterpenoid saponin. It is widely used in cosmetic and pharmaceutical applications due to its anti-inflammatory properties, and is an ingredient in foods as a sweetener additive. It has an additional attraction due to its gel forming properties at relatively low concentrations. Although it has attracted much recent attention, many of its basic surface active characteristics, adsorption and self-assembly, remain relatively unexplored. How the structure of the Glycyrrhizic acid saponin affects its surface active properties and the impact of gelation on these properties are important considerations, and to investigate these are the focus of the study.
EXPERIMENTS
In this paper the adsorption properties at the air-water interface and the self-assembly in solution have been investigated using by neutron reflectivity and small angle neutron scattering; in non-gelling and gelling conditions.
FINDINGS
The adsorption isotherm is determined in water and in the presence of gelling additives, and compared with the adsorption behaviour of other saponins. Gelation has minimal impact on the adsorption; apart from producing a rougher surface with a surface texture on a macroscopic length scale. Globular micelles are formed in aqueous solution with modest anisotropy, and are compared with the structure of other saponin micelles. The addition of gelling agents results in only minimal micelle growth, and the solutions remain isotropic under applied shear flow.
Topics: Adsorption; Glycyrrhizic Acid; Micelles; Surface Properties; Surface-Active Agents
PubMed: 33930748
DOI: 10.1016/j.jcis.2021.03.101 -
Scientific Reports Oct 2022Improving boiling is challenging due to the unpredictable nature of bubbles. One way to enhance boiling is with surfactants, which alter the solid-liquid and...
Improving boiling is challenging due to the unpredictable nature of bubbles. One way to enhance boiling is with surfactants, which alter the solid-liquid and liquid-vapor interfaces. The conventional wisdom established by previous studies suggests that heat transfer enhancement is optimized near the critical micelle concentration (CMC), which is an equilibrium property that depends on surfactant type. However, these studies only tested a limited number of surfactants over small concentration ranges. Here, we test a larger variety of nonionic and anionic surfactants over the widest concentration range and find that a universal, optimal concentration range exists, irrespective of CMC. To explain this, we show that surfactant-enhanced boiling is controlled by two competing phenomena: (1) the dynamic adsorption of surfactants to the interfaces and (2) the increase in liquid dynamic viscosity at very high surfactant concentrations. This dynamic adsorption is time-limited by the millisecond-lifetime of bubbles on the boiling surface-much shorter than the timescales required to see equilibrium behaviors such as CMC. At very high concentrations, increased viscosity inhibits rapid bubble growth, reducing heat transfer. We combine the effects of adsorption and viscosity through a simple proportionality, providing a succinct and useful understanding of this enhancement behavior for boiling applications.
Topics: Surface-Active Agents; Adsorption; Micelles; Pulmonary Surfactants; Excipients
PubMed: 36307430
DOI: 10.1038/s41598-022-21313-1 -
Pharmaceutical Development and... Jun 2023To enhance the oral bioavailability of atorvastatin calcium (ATV), a novel solidified micelle (S-micelle) was developed. Two surfactants, Gelucire 48/16 (G48) and Tween...
To enhance the oral bioavailability of atorvastatin calcium (ATV), a novel solidified micelle (S-micelle) was developed. Two surfactants, Gelucire 48/16 (G48) and Tween 20 (T20), were employed for micelle formation, and two solid carriers (SC), Florite PS-10 (FLO) and Vivapur 105 (VP105), were selected as solid carriers. The S-micelle was optimized using a Box-Behnken design with three independent variables, including G48:T20 (, 1.8:1), SC:G48 + T20 (, 0.65:1), and FLO:VP105 (, 1.4:0.6), resulting in a droplet size () of 198.4 nm, dissolution efficiency at 15 min in the pH 1.2 medium () of 47.6%, Carr's index () of 16.9, and total quantity () of 562.5 mg. The optimized S-micelle resulted in good correlation showing percentage prediction values less than 10%. The optimized S-micelle formed a nanosized dispersion in the aqueous phase, with a higher dissolution rate than raw ATV and crushed Lipitor®. The optimized S-micelle improved the relative bioavailability of oral ATV (25 mg equivalent/kg) in rats by approximately 509 and 271% compared to raw ATV and crushed Lipitor, respectively. In conclusion, the optimized S-micelle possesses great potential for the development of solidified formulations for improved oral absorption of poorly water-soluble drugs.
Topics: Rats; Animals; Atorvastatin; Micelles; Drug Delivery Systems; Biological Availability; Research Design; Chemistry, Pharmaceutical; Solubility; Emulsions; Polysorbates; Particle Size; Administration, Oral
PubMed: 37099663
DOI: 10.1080/10837450.2023.2208206 -
Journal of Pharmaceutical Sciences Mar 2023Multi-injection pharmaceutical products such as insulin must be formulated to prevent aggregation and microbial contamination. Small-molecule preservatives and nonionic...
Multi-injection pharmaceutical products such as insulin must be formulated to prevent aggregation and microbial contamination. Small-molecule preservatives and nonionic surfactants such as poloxamer 188 (P188) are thus often employed in protein drug formulations. However, mixtures of preservatives and surfactants can induce aggregation and even phase separation over time, despite the fact that all components are well dissolvable when used alone in aqueous solution. A systematic study is conducted here to understand the phase behavior and morphological causes of aggregation of P188 in the presence of the preservatives phenol and benzyl alcohol, primarily using small-angle x-ray scattering (SAXS). Based on SAXS results, P188 remains as unimers in solution when below a certain phenol concentration. Upon increasing the phenol concentration, a regime of micelle formation is observed due to the interaction between P188 and phenol. Further increasing the phenol concentration causes mixtures to become turbid and phase-separate over time. The effect of benzyl alcohol on the phase behavior is also investigated.
Topics: Poloxamer; Micelles; Scattering, Small Angle; X-Rays; X-Ray Diffraction; Surface-Active Agents; Water; Preservatives, Pharmaceutical; Phenols; Benzyl Alcohols; Solutions
PubMed: 36150467
DOI: 10.1016/j.xphs.2022.09.019 -
Current Drug Metabolism 2017In clinical studies, drugs with hydrophobic characteristic usually reflect low bioavailability, poor drug absorption, and inability to achieve the therapeutic...
In clinical studies, drugs with hydrophobic characteristic usually reflect low bioavailability, poor drug absorption, and inability to achieve the therapeutic concentration in blood. The production of poor solubility drugs, in abundance, by pharmaceutical industries calls for an urgent need to find the alternatives for resolving the above mentioned shortcomings. Poor water solubility drugs loaded with polymeric micelle seem to be the best alternative to enhance drugs solubility and bioavailability. Polymeric micelle, formed by self-assembled of amphiphilic block copolymers in aqueous environment, functioned as solubilizing agent for hydrophobic drug. This review discusses the fundamentals of polymeric micelle as drug carrier through representative literature, and demonstrates some applications in various clinical trials. The structure, characteristic, and formation of polymeric micelle have been discussed firstly. Next, this manuscript focuses on the potential of polymeric micelles as drug vehicle in oral, transdermal routes, and anti-cancer agent. Several results from previous studies have been reproduced in this review in order to prove the efficacy of the micelles in delivering hydrophobic drugs. Lastly, future strategies to broaden the application of polymeric micelles in pharmaceutical industries have been highlighted.
Topics: Antineoplastic Agents; Drug Delivery Systems; Humans; Micelles; Nanostructures; Polymers
PubMed: 27654898
DOI: 10.2174/1389200217666160921143616 -
Journal of Pharmaceutical Sciences Sep 2022Polysorbate is a key excipient included in formulations of therapeutic proteins to help prevent aggregation and surface adsorption. The stability of both polysorbate and...
Polysorbate is a key excipient included in formulations of therapeutic proteins to help prevent aggregation and surface adsorption. The stability of both polysorbate and therapeutic proteins can be compromised by oxidative degradation. In general, polysorbate is added to formulations at concentrations above the critical micelle concentration (cmc). To date, however, few experiments have quantitatively addressed the extent of extra- and intra-micellar oxidation of polysorbate in pharmaceutically relevant buffers. This study utilizes 2,2'-azobis(2-methylpropionamidine)dihydrochloride (AAPH), a peroxyl radical-generating initiator, C11-BODIPY(581/591), a lipid peroxidation probe, and fluorescence spectroscopy to reveal that both intra- and extra-micellar oxidation proceed in pharmaceutically relevant phosphate and histidine buffers. It is further demonstrated that the relative extent of oxidation observed in the intra- and extra-micellar compartments is similar irrespective of the buffer system.
Topics: Buffers; Histidine; Micelles; Oxidation-Reduction; Phosphates; Polysorbates
PubMed: 35716732
DOI: 10.1016/j.xphs.2022.06.011