Individual Micelles Research Articles

Hybrid Silica Cage-Type Nanostructures Made from Triply Hydrophilic Block Copolymers Single Micelles.

Controlling the structure and functionality of porous silica nanoparticles has been a continuous source of innovation with important potential for advanced biomedical applications. Their synthesis, however, usually involves passive surfactants or amphiphilic copolymers that do not add value to the material after synthesis. In contrast, polyion complex (PIC) micelles based on hydrophilic block copolymers allow for the direct synthesis of intrinsically functional hybrid materials. While most previous studies have focused on bulk materials made from double-hydrophilic block copolymers (DHBC), in this work we have synthesized a triple-hydrophilic block copolymer (THBC) and demonstrated both its PIC micellization and its potential for hybrid mesoporous silica nanomaterials. Introducing this THBC has allowed to direct the transition from bulk three-dimensional (3D) materials to zero-dimensional (0D) nanomaterials with cage-type structures. The stabilization and isolation of these nanostructures formed around discrete individual micelles has been made possible by the careful design of the three different blocks that each play a key role. These nanostructures could also be synthesized from hybrid PIC micelles based on THBC-multivalent metal ions complexes, offering a direct route to metal/silica composite nanoparticles. This class of THBC polymers therefore creates significant opportunities for the synthesis of nanostructures with complex and functional architectures.

Unveiling the role of solubilization of metformin hydrochloride assimilated in nonionic surfactants mediated mixed micellar assemblies

This study examines the distribution of an antidiabetic drug metformin hydrochloride (MNH) between water and mixed micellar environments produced by nonionic surfactants Tween 80 (TW-80) and Triton X-100 (TX-100). In our research, we described the UV–visible absorption spectra of a drug at various surfactant concentrations above and below critical micelle concentration (CMC). When employing TX-100, the absorbance spectra appeared to shift towards shorter wavelengths (blue shift) and there was an increase in absorbance intensity (hyperchromic shift), while using Tween 80, absorbance intensity increased (hyperchromic shift). We estimated the partition coefficient (Kx) from differential absorption data and utilized it to derive the free energy of partition (∆Gp). The partition coefficient in a single micellar system was found to be 7.82×106 and 1.79×106 in the presence of TW-80 and TX-100, respectively. The partition coefficient for the MNH/TW-80 system in a mixed micellar system reaches its maximum value of 1.08×107 when TX-100 is present at 1.26×106 M, indicating a considerable increase in the solubilizing power of micelles. The results showed that mixed micelles of TX-100/TW-80 were more effective for the solubilization of MNH than their individual micelles. It was crystal clear from the negative values of ∆Gb that binding is also spontaneous.

Synergistic Nanomedicine Delivering Topoisomerase I Toxin (SN-38) and Inhibitors of Polynucleotide Kinase 3'-Phosphatase (PNKP) for Enhanced Treatment of Colorectal Cancer.

Inhibitors of a DNA repair enzyme known as polynucleotide kinase 3'-phosphatase (PNKP) are expected to show synergistic cytotoxicity in combination with topoisomerase I (TOP1) inhibitors in cancer. In this study, the synergistic cytotoxicity of a novel inhibitor of PNKP, i.e., A83B4C63, with a potent TOP1 inhibitor, i.e., SN-38, against colorectal cancer cells was investigated. Polymeric micelles (PMs) for preferred tumor delivery of A83B4C63, developed through physical encapsulation of this compound in methoxy poly(ethylene oxide)-poly(α-benzyl carboxylate-ε-caprolactone) (mPEO-b-PBCL) micelles, were combined with SN-38 in free or PM form. The PM form of SN-38 was prepared through chemical conjugation of SN-38 to the functional end group of mPEO-b-PBCL and further assembly of mPEO-b-PBCL-SN-38 in water. Moreover, mixed micelles composed of mPEO-b-PBCL and mPEO-b-PBCL-SN-38 were used to co-load A83B4C63 and SN-38 in the same nanoformulation. The loading content (% w/w) of the SN-38 and A83B4C63 to mPEO-b-PBCL in the co-loaded formulation was 7.91 ± 0.66 and 16.13 ± 0.11% (w/w), respectively, compared to 15.67 ± 0.34 (% w/w) and 23.06 ± 0.63 (% w/w) for mPEO-b-PBCL micelles loading individual drugs. Notably, the average diameter of PMs co-encapsulating both SN-38 and A83B4C63 was larger than that of PMs encapsulating either of these compounds alone but still lower than 60 nm. The release of A83B4C63 from PMs co-encapsulating both drugs was 76.36 ± 1.41% within 24 h, which was significantly higher than that of A83B4C63-encapsulated micelles (42.70 ± 0.72%). In contrast, the release of SN-38 from PMs co-encapsulating both drugs was 44.15 ± 2.61% at 24 h, which was significantly lower than that of SN-38-conjugated PMs (74.16 ± 3.65%). Cytotoxicity evaluations by the MTS assay as analyzed by the Combenefit software suggested a clear synergy between PM/A83B4C63 (at a concentration range of 10-40 μM) and free SN-38 (at a concentration range of 0.001-1 μM). The synergistic cytotoxic concentration range for SN-38 was narrowed down to 0.1-1 or 0.01-1 μM when combined with PM/A83B4C63 at 10 or 20-40 μM, respectively. In general, PMs co-encapsulating A83B4C63 and SN-38 at drug concentrations within the synergistic range (10 μM for A83B4C63 and 0.05-1 μM for SN-38) showed slightly less enhancement of SN-38 anticancer activity than a combination of individual micelles, i.e., A83B4C63 PMs + SN-38 PMs at the same molar concentrations. This was attributed to the slower release of SN-38 from the SN-38 and A83B4C63 co-encapsulated PMs compared to PMs only encapsulating SN-38. Cotreatment of cells with TOP1 inhibitors and A83B4C63 formulation enhanced the expression level of γ-HA2X, cleaved PARP, caspase-3, and caspase-7 in most cases. This trend was more consistent and notable for PMs co-encapsulating both A83B4C63 and SN-38. The overall result from the study shows a synergy between PMs of SN-38 and A83B4C63 as a mixture of two PMs for individual drugs or PMs co-encapsulating both drugs.

Assessing the Structure and Equilibrium Conditions of Complex Coacervate Core Micelles by Varying Their Shell Composition and Medium Ionic Strength.

Complex coacervates result from an associative phase separation commonly involving oppositely charged polyelectrolytes. When this associative interaction occurs between charged-neutral diblock copolymers and oppositely charged homopolymers, a nanometric aggregate called a complex coacervate core micelle, C3M, is formed. Recent studies have addressed the issue of their thermodynamic or kinetic stability but without a clear consensus. To further investigate this issue, we have studied C3Ms formed by the combination of poly(diallyldimethylammonium) and copolymer poly(acrylamide)-b-poly(acrylate) using different preparation protocols. Dynamic light scattering and small-angle X-ray scattering measurements suggest that these structures are in an equilibrium condition because the aggregates do not vary with different preparation protocols or upon aging. In addition, their stability and structures are critically dependent on several parameters such as the density of neutral blocks in their shell and the ionic strength of the medium. Decreasing the amount of copolymer in the system and, hence, the density of neutral blocks in the shell results in an increase in the aggregate size because of the core growth, although their globular shape is retained. On the other hand, larger clusters of micelles were formed at higher ionic strengths. Partially replacing 77% of the copolymer with a homopolymer of the same charge or increasing the ionic strength of the system (above 100 mmol L-1 NaCl) leads to a metastable state, after which phase separation is eventually observed. SAXS analyses reveal that this phase separation above a certain salt concentration occurs due to the coagulation of individual micelles that seem to retain their individual globular structures. Overall, these results confirm earlier claims that equilibrium C3Ms are achieved close to 1:1 charge stoichiometry but also reveal that these conditions may vary at different shell densities or higher ionic strengths, which constitute vital information for envisioning future applications of C3Ms.

Many-body dissipative particle dynamics simulations of micellization of sodium alkyl sulfates.

We present a study of micelle formation in alkyl sulfate surfactants using the simulation method of many-body dissipative particle dynamics (MDPD). We parametrise our model by tuning the intermolecular interactions in order to reproduce experimental values for the chemical potential and density at room temperature. Using this approach, we find that our model shows good agreement with experimental values for the critical micelle concentration (CMC). Furthermore, we show that our model can accurately predict CMC trends, which result from varying properties such as surfactant tail length and the salt concentration. We apply our model to investigate the effect of aggregation number on various micellar properties, such as the shape of individual micelles and the fraction of bound counterions. We show that micelles become aspherical at large aggregation numbers, in line with experimental predictions, and that longer tail surfactants are generally more spherical at all aggregation numbers compared to those which are shorter. We find excellent agreement between our simulations and experimental values for the degree of counterion binding, a factor that is crucial to accurately studying micellar shape, but one that is typically overlooked in the existing literature.

Surface Pressure-Area Mechanics of Water-Spread Poly(ethylene glycol)-Based Block Copolymer Micelle Monolayers at the Air-Water Interface: Effect of Hydrophobic Block Chemistry.

Amphiphilic block copolymer micelles can mimic the ability of natural lung surfactant to reduce the air-water interfacial tension close to zero and prevent the Laplace pressure-induced alveolar collapse. In this work, we investigated the air-water interfacial behaviors of polymer micelles derived from eight different poly(ethylene glycol) (PEG)-based block copolymers having different hydrophobic block chemistries to elucidate the effect of the core block chemistry on the surface mechanics of the block copolymer micelles. Aqueous micelles of about 30 nm in hydrodynamic diameter were prepared from the PEG-based block copolymers via equilibration-nanoprecipitation (ENP) and spread on the water surface using water as the spreading medium. Surface pressure-area isotherm and quantitative Brewster angle microscopy (QBAM) measurements were performed to investigate how the micelle/monolayer structures change during lateral compression of the monolayer; widely varying structural behaviors were observed, including the wrinkling/collapse of micelle monolayers and deformation and/or the desorption of individual micelles. By bivariate correlation regression analysis of surface pressure-area isotherm data, it was found that the rigidity and hydrophobicity of the hydrophobic core domain, which are quantified by glass-transition temperature (Tg) and water contact angle (θ) measurements, respectively, are coupled factors that need to be taken into account concurrently in order to control the surface mechanical properties of polymer micelle monolayers; micelles having rigid and strongly hydrophobic cores exhibited high surface pressure and a high compressibility modulus under high compression. High surface pressure and a high compressibility modulus were also found to be correlated with the formation of wrinkles in the micelle monolayer (visualized by Brewster angle microscopy (BAM)). From this study, we conclude that polymer micelles based on hydrophobic block materials having higher Tg and θ are more suitable for surfactant replacement therapy applications that require the therapeutic surfactant to produce a high surface pressure and modulus at the alveolar air-water interface.

Liposome-Micelle-Hybrid (LMH) Carriers for Controlled Co-Delivery of 5-FU and Paclitaxel as Chemotherapeutics.

Paclitaxel (PTX) and 5-fluorouracil (5-FU) are clinically relevant chemotherapeutics, but both suffer a range of biopharmaceutical challenges (e.g., either low solubility or permeability and limited controlled release from nanocarriers), which reduces their effectiveness in new medicines. Anticancer drugs have several major limitations, which include non-specificity, wide biological distribution, a short half-life, and systemic toxicity. Here, we investigate the potential of liposome-micelle-hybrid (LMH) carriers (i.e., drug-loaded micelles encapsulated within drug-loaded liposomes) to enhance the co-formulation and delivery of PTX and 5-FU, facilitating new delivery opportunities with enhanced chemotherapeutic performance. We focus on the combination of liposomes and micelles for co-delivery of PTX and 5_FU to investigate increased drug loading, improved solubility, and transport/permeability to enhance chemotherapeutic potential. Furthermore, combination chemotherapy (i.e., containing two or more drugs in a single formulation) may offer improved pharmacological performance. Compared with individual liposome and micelle formulations, the optimized PTX-5FU-LMH carriers demonstrated increased drug loading and solubility, temperature-sensitive release, enhanced permeability in a Caco-2 cell monolayer model, and cancer cell eradication. LMH has significant potential for cancer drug delivery and as a next-generation chemotherapeutic.

Functional amyloid in a lipid-like environment: a merry dance of many steps.

Functional amyloid, which unlike its pathological counterpart serves a biological purpose, is produced in a carefully orchestrated sequence of events. In bacteria, the major amyloid component is transported over the periplasm and through the outer membrane to assemble on the bacterial cell surface. During its life time, the amyloid protein may be exposed to both membrane lipids and extracellular surfactant, making it relevant to study its interactions with these components in vitro. Particularly for charged surfactants, the interaction is quite complex and highly dependent on the surfactant:protein molar ratio. Low ratios typically promote aggregation, likely by binding the proteins to micelles and thus increasing the local concentration of proteins, while higher concentrations see an inhibition of the same process as the protein is diluted out and immobilized on individual micelles. This is particularly pronounced for strongly anionic surfactants like SDS; the naturally occurring biosurfactant rhamnolipid interacts more weakly with the protein, which still not only allows aggregation but also leads to less detrimental effects at higher ratios. Similarly, anionic vesicle-forming lipids largely stimulate aggregation likely because of weaker interactions. Anionic lysolipids, thanks to their micelle-forming properties, resemble SDS in their impact on fibrillation. There are also examples of systems where membrane binding sequesters an otherwise amyloidogenic sequence and prevents fibrillation or-quite the opposite- liberates another part of the protein to engage in self-assembly. Thus, membranes and surfactants have very varied roles to play in the biogenesis and function of bacterial amyloid.

Interplay of temperature and calcium content in beta-casein solutions: From controlled self-aggregation of micelles in bulk to the design of stable foams

We describe in this study the aggregation behaviour of β-casein micelles from milk in bulk aqueous solution as function of both temperature and calcium content, and its influence on the foaming properties, in order to test if the different aggregation states of β-casein makes possible the design of proteins-based thermoresponsive foams. First, we characterized the morphology of the self-assembled β-casein molecules in solution by coupling turbidity measurements, Dynamic Light Scattering and Small Angle Neutron Scattering. They self-organize into individual micelles at low temperature (20°C) whatever the calcium content, and transit in a reversible way into aggregates of micelles at large temperature in presence of calcium, with a threshold transition that depend both on temperature and calcium content. The micelles aggregation is driven by the calcium through association with serine phosphate groups localized on the hydrophilic part of the β-casein. In the micelles regime, we demonstrated that the addition of calcium tunes the aggregation number of unimers per micelle in the same way than an increase of temperature through a change of hydrophobic interactions. The hydrophilic chains of the corona are however in a good solvent and interact through excluded volume interactions, even when the β-casein micelles aggregates themselves. The internal molecular structure of the micelles is thus not modified by calcium bridges, which explains the complete reversibility of the aggregation process over temperature cycling. Second, we studied the foam stability versus time as a function of the temperature and calcium content by measuring the kinetic evolution of both the foam volume and the liquid fraction. Foams produced by solutions containing only β-casein micelles were stable in terms of foam volume on a timescale of 1 h at 20°C but drained quickly. However, foams become unstable when the temperature was increased above 20°C. In presence of calcium, the aggregation of β-casein micelles inside the foam liquid channels enabled to increase foam stability at larger temperature by acting as a cork, which slows down the drainage. The increase of foam stability by such aggregates is however not sufficient on the long term to allow the design of thermoresponsive foams.

Hierarchical Approach for Controlled Assembly of Branched Nanostructures from One Polymer Compound by Engineering Crystalline Domains.

The interplay of crystalline packing, which governs atomic length-scale order, and hierarchical assembly, which governs longer length scales, is essential to fabricate complex superstructures from polymers for many applications. Here, we demonstrate that a diblock copolymer containing an N-octylglycine peptoid block, which has a propensity to crystallize, can form distinct hierarchical superstructures including a star-like morphology, a superbrush, or a nanosheet by tuning the balance between surface energy arising from the solubility of the copolymers and crystallization energy of the solvophobic polypeptoid blocks. We show that partially ordered micellar aggregates (clusters) are key intermediates that form early in the assembly process and template the formation of superstructures via the oriented fusion of individual micelles as the growth materials. Notably, the fiber-like branch of the superstructures is driven by crystallization and exhibits growth in a living linear manner. The superstructures can be internalized by mammalian cells and hold promise for biomedical applications.

Interaction of nanoparticles with non-spherical micelles and bilayers

Interaction of different-sized anionic silica nanoparticles with non-spherical micelles and bilayers of non-ionic surfactant C12E10 has been studied by small-angle neutron scattering (SANS). The non-ionic surfactant C12E10 in aqueous solution self-assembles to form core–shell spherical micelles. Different means (temperature, salts, and alcohols) have been examined to induce the structural transition of micelles from spherical to non-spherical and bilayer formation. The dehydration from micellar shell leads to such transition in the cases of increasing temperature and selective salt (e.g., KF). On the other hand, for alcohols, spherical to non-spherical micellar transition or bilayer formation arises for long-chain length alcohols CnOH (n > 5) because of the mixed micelles formation of alcohol with surfactant. From the different ways to alter the micellar morphology, transitions obtained by alcohols were found to be the best suited for nanoparticle–surfactant solution as they do not influence the interactions between nanoparticle and surfactant and among nanoparticles. It is found that the shorter chain length alcohols (CnOH, n ≤ 5) interact with nanoparticles via the adsorption of individual micelles while the non-spherical micelles and bilayers of surfactant formed in the presence of long-chain length alcohols rearrange themselves to attach onto the nanoparticles. SANS with an advantage of contrast variation (contrast matching silica nanoparticles with solvent) provides the evidence of bilayer formation around nanoparticles. The concentration effect of long-chain length alcohol on micelle morphology and subsequently on the nanoparticle–surfactant system is also examined. It is found that the adsorption of surfactant bilayer structures is prominent in the case of larger particle size due to flattened curvature.

Electrochemical observation of individual collision-blocking events of TX-100 nanomicelles: An accurate and universal approach for the critical micelle concentration determination of surfactants

The electrochemical collision-blocking technique, equipped with the nanoelectrode of Pt was proposed for determination of the critical micelle concentration (CMC) of non-ionic surfactant TX-100. The approach was found on detection of individual collided nanomicelles in amperometric measurements of the oxidation of K4Fe(CN)6 varying the titrated concentration of TX-100 whereas the formed micelles above the CMC stick on the electrode surface during collision to locally block the flux of electroactive species and further to change the faradaic current. The step-like current transients observed in i-t curves have been demonstrated corresponding to electrochemical collision events of individual TX-100 micelles and micelle aggregates by 3D COMSOL simulations. The logarithm relations between the collision frequency of micelle(s) and the concentration of TX-100 were derived by regression analysis to give the corresponding values of CMC in salt solutions. Further, an ‘ideal’ CMC of TX-100 without influence of additional salts was estimated to be 0.194 mM using the McDevit-Long theory. The more accurate CMC determined in this work has shown less than the previously reported, mainly due to the detection limit for micelle as low as 0.41 fM. Also, we determined the second CMC of 1.21 mM as the first observation of the collision response of micelle aggregates during TX-100 titration. Owing to its analytical characteristics in single-particle tracking and material insensitivity, the approach we proposed is potentially to be a universal tool for accurate determination of CMC of surfactants, and also for studying the formation of polymer particles at a single-particle level, which is not easily accessible using conventional ensemble measurements.

Complex Micellization Behavior of the Polysorbates Tween 20 and Tween 80.

Polysorbates (PSs, Tweens) are widely used surfactant products consisting of a sorbitan ring connecting up to four ethylene oxide (EO) chains of variable lengths, one or more of which are esterified with fatty acids of variable lengths and saturation degrees. Pharmaceutical applications include the stabilization of biologicals in solutions and the solubilization of poorly water soluble, active ingredients. This study characterizes the complex association behavior of compendial PSs PS20 and PS80, which is fundamentally different from that of single-component surfactants. To this end, a series of demicellization experiments of isothermal titration calorimetry with different PS concentrations are evaluated. Their experiment-dependent heats of titration are converted into a common function of the state of a sample, the micellar enthalpy Qm(c). These functions demonstrate that initial micelles are already present at the lowest concentrations investigated, 2 μM for PS20 and 10 μM for PS80. Initial micelles consist primarily of the surfactant species with the lowest individual critical micelle concentration (cmc). With increasing concentration, the other PS species gradually enter these micelles in the sequence of increasing individual cmc's and hydrophilic-lipophilic balance. Concentration ranges with pronounced slopes of Qm(c) can be tentatively assigned to the uptake of the major components of the PS products. Micellization and the variation of the micelle properties progress up to at least 10 mM PS. That means the published cmc values or ranges of PS20 and PS80 may be related to certain, major components being incorporated into and forming specific micelles but must not be interpreted in terms of an absence of micelles below and constant properties, e.g., the surface activity, of the micelles above these ranges. The micellization enthalpy curves differ quite substantially between PS20 and PS80 and, in a subtler fashion, between individual quality grades such as high purity, pure lauric acid/pure oleic acid, super-refined, and China grade.

Cooperative organizations of small molecular surfactants and amphiphilic block copolymers: Roles of surfactants in the formation of binary co‐assemblies

AbstractThe construction of highly ordered organizations through self‐assembly is one of the most popular phenomena both in natural and artificial environments. Amphiphilic molecules are the most commonly used building blocks for the self‐assembly, which are conventionally known as amphiphilic low molecular weight surfactants with polar heads and nonpolar tails, or amphiphilic block copolymers (BCPs) consisting of covalently bonded hydrophilic and hydrophobic block chains. Compared with single surfactant self‐assembly system, binary amphiphiles co‐assembly systems composing of both small mass surfactants and amphiphilic BCPs feature high flexibilities and versatilities in materials designing and structure regulation, ascribing to the vast possibilities of intermolecular interactions within the systems and facile component modulations during the assembly processes. The amphiphilic features of the two kinds of molecules endow them with similar self‐assembly behaviors, while the unique and distinct characters of each kind of amphiphiles lead to various complex but highly diversified co‐assembly systems. According to the roles of the surfactant played in the co‐assembly system, in this review, we summarize the binary co‐assembly systems from three distinct types: 1) the co‐micellization system in which the surfactants are added into the BCPs assemblies as a self‐assembly assistant; 2) the co‐emulsification system in which the surfactants work as an emulsion stabilizer to assist and confine the assembly of BCPs in 3D geometries; 3) the co‐templating system where the individual micelles of both surfactant and BCPs are hierarchically arranged and distributed to guide the formation of hierarchical nanomaterials. Following this, the major potential applications of the nanomaterials synthesized from the binary amphiphiles in biological field are described. Finally, we shortly discuss the current challenges and future perspectives of the binary amphiphiles self‐assembly systems.

Mixed micelle formation between a surface active ionic liquid and tricyclic antidepressant drugs (imipramine hydrochloride and amitriptyline hydrochloride)

Mixed micelle formation between surface active ionic liquid (1-dodecyl-3-methylimidazolium bromide, IL) and two amphiphilic drugs consisting of imipramine hydrochloride (IMP) and amitriptyline hydrochloride (AMT) were investigated in different mole fractions at 298 K using electrical conductivity measurements. The experimental results of mixed antidepressant drugs (IMP and AMT) with ionic liquid in aqueous solution indicated that CMC values decreased with the addition ionic liquid in mixture. Also, the CMC values in AMT/IL system are comparatively lower than those found in IMP/IL system, which indicates that the formation of mixed micelle is more favorable in presence of AMT. The different theoretical models (Clint, Rubingh, Motomura and Rodenas) were used to evaluate the micellar mole fractions (Xi), interaction parameter (βm) and activity coefficients of components (f1 and f2) in the mixed micelle. In both studied systems, the values of interaction parameter suggest the synergistic effects in mixed state. Activity coefficients are less than unity which means non-ideal mixing. Also, the excess free energy of micellization (ΔGex) values have been estimated using activity coefficients at different compositions. This parameter not only confirm that mixed micellization is spontaneous in nature but also is extra stable than individual micelle.

Correlations between the solubility and surface characteristics of milk protein concentrate powder particles

The solubility of high-protein milk protein concentrate (MPC) may decrease significantly during storage, particularly at relatively high temperatures and humidity. The objective of this study was to seek correlations between the solubility loss of MPC during storage and various surface characteristics determined on the basis of simultaneous nanoscale topographical imaging and nanomechanical mapping of MPC particle surfaces using atomic force microscopy. A control MPC and a calcium-depleted MPC were stored at 45°C and 66% relative humidity for up to 60 d. The solubility of the control MPC was 56% at the beginning of the storage and gradually decreased to 10% at the end of the 60-d storage. The calcium-depleted MPC exhibited more rapid decreases from almost 100% at the beginning of the storage to 18% after storage for 45 d, after which we observed no significant difference in solubility between the control and calcium-depleted MPC. Averaged or root mean squared roughness values calculated using topographical images were found to have no correlation with the solubility. Deformation, Derjaguin-Muller-Toropov modulus, and adhesion images revealed the presence of individual casein micelles and larger clusters of aggregated casein micelles at MPC particle surfaces, whereas we observed no correlation between the solubility and averaged values of these nanomechanical properties. Furthermore, Derjaguin-Muller-Toropov modulus and adhesion images showed that the peripheral edges of individual casein micelles and their clusters had significantly higher values of the corresponding nanomechanical properties than other regions in the images, indicating the occurrence of the fusion of casein micelles. The surface area coverage or the percent area of the fused regions in an image revealed significant negative linear correlations with the solubility for both the control and calcium-depleted MPC. The present results support the hypothesis that the fusion of casein micelles at MPC powder particle surfaces is a causative factor for the solubility loss of MPC during storage and in turn suggest that the solubility loss may be alleviated by inhibiting the formation of a crust or skin on powder particle surfaces.

Unexpected thermo-responsiveness of bisurea-functionalized hydrophilic polymers in water

HypothesisThermoresponsive polymers are important materials for various applications. However, the number of polymers that exhibit this property in the temperature range of interest remains limited. The development of novel rational design strategies through the understanding of the thermal transition’s origin is therefore of utmost importance. ExperimentsBisurea-functionalized water-soluble polymers were synthesized by RAFT polymerization. After direct dissolution in water, the supramolecular assemblies were analyzed by cryo-TEM and SANS. Their temperature-dependent water-solubility was characterized by various techniques, namely DLS, SANS, DSC, IR, to understand the origin of the temperature sensitivity. FindingsThe supramolecular assemblies exhibit an unexpected temperature-dependent solubility. For instance, a cloud point of only 39 °C was measured for poly(N,N-dimethylacrylamide) assemblies. This property is not restricted to one specific polymer but is rather a general feature of bisurea-functionalized polymers that form supramacromolecular bottlebrushes in water. The results highlight the existence of two distinct transitions; the first one is a visually perceptible cloud point due to the aggregation of individual micelles, presumably driven by the hydrophobic effect. The second transition is related to the dissociation of intermolecular bisurea hydrogen bonds. Finally, we show that it is possible to widely tune the cloud point temperature through the formation of co-assemblies.

Solubilization of hydrophobic drugs clozapine and oxcarbazepine in the lower and higher molecular weight pluronic mixed micelles-a physicochemical, In vitro release and In vitro anti-oxidant study

In this work, we studied the solubilization capacityof the hydrophobic drugs Clozapine (CLZ) and Oxcarbazepine (OXC) in mixed micelles of low molecular weight pluronics (L64 and L35) and high molecular weight pluronics (P84, F127, F68 and P123) using UV–visible spectroscopy. The drug solubility, drug loading efficiency, the micelle–water partition coefficient (P), and Gibbs free energy (ΔG°) of solubilization were measured. From the obtained results, we concluded that the highest solubility of CLZ was observed in binary mixture of L64/P84 (1:4) due to the hydrophobic nature of these pluronics. In the case of OXC, the highest solubility was observed in L64/F127(1:4)because the drug solubilized both in the core and the corona region of F127 since OXC contains a carboxamide polar moiety. Fluorescence spectroscopy indicated that the critical micelle concentration (cmc) decreased with the formation of mixed micelles as compared to pure individual micelles. From DLS measurements, it was observed that there was an increase in size of mixed micelles from mixed micelles to drug (CLZ and OXC) loaded mixed micelles. In vitro release study of CLZ showed that as the amount of P84 in binary mixed micelles decreases, the release was faster. The formulations were also screened for antioxidant activity by four different methods. The antioxidant activity was significantly increased in the binary mixture of the pluronic solutions, indicated that pluronic formulations can be considered as an effective drug delivery candidate in the management of diseases that affect the central nervous system.

Micellar Extraction Preconcentration and Colorimetric Determination of Some Phenols

We studied the extraction and preconcentration of phenol and its hydroxy derivatives using individual and mixed micelles of nonionic and cationic surfactants with the digital recording of the analytical signal. This approach is based on the color reaction of phenols with diazotized 4-nitroaniline and micellar extraction of the products of their interaction (azo compound). The micellar extraction parameters (pH, the concentration of reagents, NaOH, and ethanol) were optimized for the efficient extraction of azo compounds of the studied phenols. The proposed method enables the determination of phenol and resorcinol at the MPC level with an error not exceeding 10%. For a qualitative assessment of the presence of phenols, the geometric parameters (area S, perimeter P) of the corresponding radar plots were used along with colorimetric parameters (R, G, B). The calibration dependences are linear within 1 × 10–7–3 × 10–5 M for phenol and 1 × 10–7–2 × 10–5 M for resorcinol and phloroglucinol. The developed colorimetric method was tested in the determination of resorcinol in the Rezortsinol pharmaceutical preparation.

Amphiphilic Copolymers of Acrylic Acid and n-Butyl Acrylate with the Predetermined Microstructure: Synthesis and Properties

Features of the synthesis of n-butyl acrylate copolymers with acrylic acid in 1,4-dioxane by free radical reversible addition-fragmentation chain transfer (RAFT) polymerization mediated by symmetric trithiocarbonates are considered. It is shown that the living mechanism of polymerization is realized in the studied systems. The chemical nature of the RAFT agent dictates different chain microstructures (random block or random) of the copolymers. The effect of chain microstructure on the properties of the copolymers containing about 90 mol % of acrylic acid units is studied by differential scanning calorimetry, contact angle measurements, turbidimetry, potentiometric titration, and dynamic light scattering. It is demonstrated that all the copolymers in the solid phase have similar properties: a single glass transition temperature close to the glass transition temperature of polyacid and a good water wettability. In dilute aqueous solutions, the properties of the copolymers are different: at the inherent pH, random copolymer macromolecules form large associates, while random block copolymers are dispersed into individual coils or micelles. All the copolymers are weaker polyacids compared with PAA; the random block copolymers are characterized by the compaction of macromolecules at small degrees of ionization. Our studies provide evidence that reversible addition-fragmentation chain transfer polymerization is an efficient tool for the targeted insertion of nonpolar units into a polyelectrolyte chain and it can be used for the fine-tuning of its properties.