Formation Of Colloidal Structures Research Articles

Amphotericin B and monoacyl-phosphatidylcholine form a stable amorphous complex

Amphotericin B (AmB) is a “life-saving” medicine for the treatment of invasive fungal infections and visceral leishmaniasis. To date, all marketed AmB formulations require parenteral administration, which causes high rates of acute infusion-related side effects and dose-dependent nephrotoxicity. The development of an oral AmB formulation will entail numerous advantages including increased patient compliance, eliminated infusion-related toxicities and reduced nephrotoxicity. Unfortunately, the gastrointestinal absorption of AmB is negligible due to its extremely low solubility in both aqueous and lipid solvents, and its poor gastrointestinal permeability. Drug-phospholipid complexation is an emerging strategy for oral delivery of poorly soluble drugs. In this study, monoacyl-phosphatidylcholine (MAPC) was complexed with AmB forming an AmB-MAPC complex (APC), to enhance the dissolution rate and aqueous solubility of AmB, in order to enable oral delivery of AmB. X-ray powder diffraction demonstrated that AmB was transformed to its amorphous form following complexation with MAPC, i.e. in the APC. Fourier-transform infrared spectroscopy suggested molecular interactions between AmB and MAPC. Dynamic light scattering indicated formation of colloidal structures after aqueous dispersion of APC; Cryogenic transmission electron microscopy showed that APC formed small round, “rod-like” and “worm-like” micellar structures and Small-angle neutron scattering provided three-dimensional micellar structures formed by APC upon aqueous dispersion, which indicated that AmB was inserted into the micellar mono-layer membrane formed by MAPC. Additionally, APC showed an increased dissolution rate and a higher amount of AmB solubilized in fasted state simulated intestinal fluid, compared to AmB/MAPC physical mixtures and crystalline AmB. In conclusion, an APC exhibiting amorphous properties was developed, the APC showed improved dissolution rate and increased apparent aqueous solubility compared to AmB, indicating that the application of APC could be a promising strategy to enable the oral delivery of AmB.

Reversible and spatiotemporal control of colloidal structure formation

Tuning colloidal structure formation is a powerful approach to building functional materials, as a wide range of optical and viscoelastic properties can be accessed by the choice of individual building blocks and their interactions. Precise control is achieved by DNA specificity, depletion forces, or geometric constraints and results in a variety of complex structures. Due to the lack of control and reversibility of the interactions, an autonomous oscillating system on a mesoscale without external driving was not feasible until now. Here, we show that tunable DNA reaction circuits controlling linker strand concentrations can drive the dynamic and fully reversible assembly of DNA-functionalized micron-sized particles. The versatility of this approach is demonstrated by programming colloidal interactions in sequential and spatial order to obtain an oscillatory structure formation process on a mesoscopic scale. The experimental results represent an approach for the development of active materials by using DNA reaction networks to scale up the dynamic control of colloidal self-organization.

Complex colloidal structures with non-linear optical properties formed in an optical trap.

Illumination of a colloidal suspension of dielectric nanoparticles (50 nm in radius) with counter-propagating non-interfering laser beams of sufficient power leads to spatial redistribution of particles due to associated optical forces and formation of colloidal structures composed of thousands of nanoparticles along the beams. We employ a weak probe beam propagating through the colloidal structure and demonstrate that the colloidal structure acts effectively as a non-linear optical medium, similar to a gradient index lens, with optical transformation properties externally tunable by trapping laser power. With an increasing number of nanoparticles we observe the formation of a more complex colloidal structure axially and even laterally and we explain the origin of this process.

Effect of the microstructure of n-butyl acrylate/N-isopropylacrylamide copolymers on their thermo-responsiveness, self-organization and gel properties in water

HypothesisPolymer composition, microstructure, molar mass, architecture… critically affect the properties of thermoresponsive polymers in aqueous media. ExperimentsThe behaviour of n-isopropylacrylamide and n-butyl acrylate-based copolymers of variable composition and structure (statistical, diblock or triblock) was studied in solution at different temperatures and concentrations with turbidimetry measurements, differential scanning calorimetry, electronic microscopy, rheology and scattering experiments. FindingsThis study illustrates how it is possible through chemical engineering of the microstructure of amphiphilic thermoresponsive polymers to modulate significantly the self-assembly, morphological and mechanical properties of these materials in aqueous media. Statistical structures induced a strong decrease of cloud point temperature compared to block structures with similar composition. Moreover, block structures lead below the transition temperature to the formation of colloidal structures. Above the transition temperature, the formation of colloidal aggregates is observed at low concentrations, and at higher concentrations the formation of gels. Neutron scattering and light scattering measurements show that for a given composition diblock structures lead to smaller colloids and mesoglobules than their triblock counterparts. Moreover, diblock structures, compared to triblock analogs, allow the formation of gels that do not demix with time (no synaeresis) but that are softer than triblock gels.

Nanostructure generation during milk digestion in presence of a cell culture model simulating the small intestine

HypothesisThe development of advanced oral delivery systems for bioactive compounds requires the fundamental understanding of the digestion process within the gastrointestinal tract. Towards this goal, dynamic invitro digestion models, capable of characterising the molecular as well as colloidal aspects of food, together with their biological interactions with relevant invitro cell culture models, are essential. ExperimentsIn this study, we demonstrate a novel digestion model that combines flow-through time resolved small angle X-ray scattering (SAXS) with an invitro Caco-2/HT-29 cell co-culture model that also contained a mucus layer. This set-up allows the dynamic insitu characterisation of colloidal structures and their transport across a viable intestinal cell layer during simulated digestion. FindingsAn integrated online SAXS – invitro cell co-culture model was developed and applied to study the digestion of nature’s own emulsion, milk. The impact of the invitro cell culture on the digestion-triggered formation and evolution of highly ordered nanostructures in milk is demonstrated. Reported is also the crucial role of the mucus layer on top of the cell layer, protecting the cells from degradation by digestive juice components such as lipase. The novel model can open unique possibilities for the dynamic investigation of colloidal structure formation during lipid digestion and their effect on the uptake of bioactive molecules by the cells.

Interactions of Artefenomel (OZ439) with Milk during Digestion: Insights into Digestion-Driven Solubilization and Polymorphic Transformations.

Milk has been used as a vehicle for the delivery of antimalarial drugs during clinical trials to test for a food effect and artefenomel (OZ439) showed enhanced oral bioavailability with milk. However, the nature of the interaction between milk and OZ439 in the gastrointestinal tract remains poorly understood. To understand the role of milk digestion on the solubilization of OZ439 and polymorphism, we conducted real-time monitoring of crystalline drug in suspension during in vitro intestinal lipolysis of milk containing OZ439 using synchrotron X-ray scattering. OZ439 formed an unstable solid-state intermediate free base form (OZ439-FB form 1) at intestinal pH and was partially solubilized by milk fat globules prior to lipolysis. Dissolution of the free base form 1 and recrystallization of OZ439 in a more stable polymorphic form (OZ439-FB form 2) occurred during in vitro lipolysis in milk. Simply stirring the milk/drug suspension in the absence of lipase or addition of lipase to OZ439 in a lipid-free buffer did not induce this polymorphic transformation. The formation of OZ439-FB form 2 was therefore accelerated by the solubilization of OZ439-FB form 1 during the digestion of milk. Our findings confirmed that although crystalline precipitates of OZ439-FB form 2 could still be detected after in vitro digestion, milk-based lipid formulations provided a significant reduction in crystalline OZ439 compared to lipid-free formulations, which we attribute to the formation of colloidal structures by the digested milk lipids. Milk may therefore be particularly suited as a form of lipid-based formulation (LBF) for coadministration with OZ439, from which both an enhancement in OZ439 oral bioavailability and the delivery of essential nutrients should result.

Curvature capillary repulsion

Directed assembly of colloids is an exciting field in materials science for forming structures with new symmetries and responses. We have been studying how interface curvature can be used in to guide colloidal structure formation. On a fluid interface, the area of the deformation field around adsorbed microparticles depends on interface curvature; particles move to minimize the excess area of the distortions that they make in the interface. For particles that are sufficiently small, this area decreases as particles move along principal axes to sites of high deviatoric curvature. We have studied this migration for microparticles on a curved host interface with zero mean curvature created by pinning an oil-water interface around a micropost. Here, on a similar interface, we demonstrate capillary curvature repulsion; that is, we identify conditions in which microparticles migrate away from high curvature sites. Using theory and experiment, we discuss the origin of these interactions and their relationship to the particle's undulated contact line. We discuss the implications of this type of interaction in various contexts from materials science to microrobotics.Received 30 June 2017DOI:https://doi.org/10.1103/PhysRevFluids.2.100501©2017 American Physical SocietyPhysics Subject Headings (PhySH)Research AreasCapillary interactionsSelf-assemblySurface & interfacial phenomenaPhysical SystemsColloidsLiquid-liquid interfacesTechniquesLithographyOptical microscopySputteringFluid DynamicsPolymers & Soft MatterParticles & Fields

Characterization of titanium dioxide nanoparticle removal in simulated drinking water treatment processes

This study characterized the fate of nano-TiO2 in both powder (TiO2(P)) and suspension (TiO2(S)) forms in simulated drinking water treatments. Nano-TiO2 solutions of 0.1, 1.0, and 10mg/L were prepared with deionized water and raw waters from the Changxing and Fengshan Water Treatment Plants in Taiwan to assess the effects of water matrices on nano-TiO2 behavior during water treatment. After the laboratory simulated water treatment, including pre-chlorination, coagulation, sedimentation, filtration and post-chlorination, the residual Ti concentration ranged from 2.7 to 47.4% in different treatment units and overall removal efficiency was between 52.6% and 97.3% in all cases except for nano-TiO2 at concentration of 0.1mg/L. Overall removal efficiency for the TiO2 at 10mg/L concentration ranged from 9.3 to 53.5%. Sedimentation (after coagulation) and filtration were the most important processes for removing nano-TiO2 due in part to particle agglomeration, which was confirmed by size distribution and zeta potential measurements. The size of nano-TiO2 increased from 21–36nm to 4490nm in the supernatant after sedimentation, and subsequent filtration treatment further removed all agglomerates at size >1μm. Zeta potential revealed interactions between nano-TiO2 particles and anionic functional groups or negatively-charged natural organic matters, leading to a decrease in surface charge. After sedimentation and filtration, the zeta potential of supernatants and filtrates were close to zero, meaning the absence of nanoparticles. The highest Ti removal after sedimentation occurred in Fengshan raw water due to higher ionic strength and coagulant dosage applied. On the other hand, the surfactant additives in TiO2(S) promoted dispersion of nano-TiO2 particles, which in turn led to lower particle removal. SEM images of nanoparticles after chlorination or coagulation revealed the coverage of nano-TiO2 particles by viscous substances and formation of colloidal structures.

Inclusion of Digestible Surfactants in Solid SMEDDS Formulation Removes Lag Time and Influences the Formation of Structured Particles During Digestion.

Solid self-microemulsifying drug delivery systems (SMEDDS) have received considerable attention in recent times attempting to overcome the drawbacks of liquid SMEDDS. Earlier literature reports on solid SMEDDS have focussed on formulation development; however, the digestibility and propensity for self-assembly of the digested components with endogenous bile salts and phospholipids are unknown. Therefore, as a starting point, previously reported solid SMEDDS containing Gelucire® 44/14 (GEL) and the non-digestible surfactants, Vitamin E TPGS (TPGS) and Lutrol® F 127 (F 127), were prepared, and their dispersion and digestion behaviours were studied using an in vitro lipolysis model, coupled with small-angle X-ray scattering (SAXS) to determine the formed colloidal structures during digestion in real time. GEL alone was digested (89%) and formed a lamellar phase (Lα). When surfactants were added at a 40:60% w/w lipid to surfactants ratio, digestion was inhibited with a significant lag time being evident. However, increasing the fraction of GEL to 50% w/w enabled digestion with reduced lag time. The substitution of the non-digestible surfactants with digestible surfactants, sucrose esters S-1670 (S-1670) and Span® 60 (S-60), eliminated the digestion lag time, and the formation of colloidal structures was more similar to that of GEL alone.

Colloidal particles as elastic triads in nematic liquid crystals

ABSTRACTIn this short review we summarise already published results to manifest very important role of high order elastic terms in the formation of colloidal structures in nematic liquid crystals (NLC). We reveal that every colloidal particle in nematics can be effectively represented as a triad of nonzero elastic moments. Usually colloidal particles in NLCs are treated with their elastic dipole and/or quadrupole moments only. But we demonstrate that octupole, hexadecapole and even 64-pole moments play an important role as well and determine parameters of different 1D, 2D and even 3D colloidal crystals in NLCs. In general the triad of the first three nonzero elastic moments can describe almost all colloidal structures observed so far. Dipole particles should be considered as hard spheroids with a triad of the dipole, quadrupole and octupole moments. Quadrupole particles should be treated as hard spheres with a triad of quadrupole, hexadecapole and 64-pole elastic momentsPACS numbers: 61.30.Dk, 82.70.Dd, 64.70.M−

Kinetically guided colloidal structure formation

The self-organization of colloidal particles is a promising approach to create novel structures and materials, with applications spanning from smart materials to optoelectronics to quantum computation. However, designing and producing mesoscale-sized structures remains a major challenge because at length scales of 10-100 μm equilibration times already become prohibitively long. Here, we extend the principle of rapid diffusion-limited cluster aggregation (DLCA) to a multicomponent system of spherical colloidal particles to enable the rational design and production of finite-sized anisotropic structures on the mesoscale. In stark contrast to equilibrium self-assembly techniques, kinetic traps are not avoided but exploited to control and guide mesoscopic structure formation. To this end the affinities, size, and stoichiometry of up to five different types of DNA-coated microspheres are adjusted to kinetically control a higher-order hierarchical aggregation process in time. We show that the aggregation process can be fully rationalized by considering an extended analytical DLCA model, allowing us to produce mesoscopic structures of up to 26 µm in diameter. This scale-free approach can easily be extended to any multicomponent system that allows for multiple orthogonal interactions, thus yielding a high potential of facilitating novel materials with tailored plasmonic excitation bands, scattering, biochemical, or mechanical behavior.

Influence of surface modification on structure formation and micromechanical properties of spray-dried silica aggregates

Spray drying processes were utilized for the production of hierarchical materials with defined structures. The structure formation during the spray drying process and the micromechanical properties of the obtained aggregates depend on the particle–particle interactions, the primary particle size and morphology as well as the process parameters of the spray drying process. Hence, the effect of different primary particle systems prepared as stable dispersions with various surface modifications were investigated on the colloidal structure formation and the micromechanical properties of silica particles as model aggregates and compared to theoretical considerations. The obtained results show that the structure formation of aggregates during the spray drying process for stable suspensions is almost independent on the functional groups present at the particle surface. Further, the mechanical properties of these aggregates differ considerably with the content of the bound ligand. This allows the defined adjustment of the aggregate properties, such as the strength and surface properties, as well as the formation of defined hierarchical aggregate structures.

How relevant are assembled equilibrium samples in understanding structure formation during lipid digestion?

Lipid-based formulations are gaining interest for use as drug delivery systems for poorly water-soluble drug compounds. During digestion, the lipolysis products self-assemble with endogenous surfactants in the gastrointestinal tract to form colloidal structures, enabling enhanced drug solubilisation. Although earlier studies in the literature focus on assembled equilibrium systems, little is known about structure formation under dynamic lipolysis conditions. The purpose of this study was to investigate the likely colloidal structure formation in the small intestine after the ingestion of lipids, under equilibrium and dynamic conditions. The structural aspects were studied using small angle X-ray scattering and dynamic light scattering, and were found to depend on lipid composition, lipid chain length, prandial state and emulsification. Incorporation of phospholipids and lipolysis products into bile salt micelles resulted in swelling of the structure. At insufficient bile salt concentrations, a co-existing lamellar phase was observed, due to a reduction in the solubilisation capacity for lipolysis products. Emulsification accelerated the rate of lipolysis and structure formation.

Iron binding to caseins in the presence of orthophosphate

As adding >5mM ferric chloride to sodium caseinate solutions results in protein precipitation, the effects of orthophosphate (0–64mM) addition to sodium caseinate solution (2% w/v protein) on iron-induced aggregation of the caseins were studied at pH 6.8. Up to 20mM ferric chloride could be added to sodium caseinate solution containing 32mM orthophosphate without any protein precipitation. The addition of iron to sodium caseinate solution containing orthophosphate reduced the diffusible phosphorus content in a concentration-dependent manner. Added iron appeared to interact simultaneously with phosphoserine on the caseins and inorganic phosphorus. The relative sizes of the casein aggregates were governed by the concentration of orthophosphate and the aggregates consisted of all casein fractions, even at the lowest level of ferric chloride addition (5mM). It is hypothesised that the addition of iron to caseins in the presence of orthophosphate results in the formation of colloidal structures involving casein–iron–orthophosphate interactions.

Immobilised Lipase for In Vitro Lipolysis Experiments

In vitro lipolysis experiments are used to assess digestion of lipid-based formulations, and probe solubilisation by colloidal phases during digestion. However, proteins and other biological components in the pancreatin often used as the lipase result in high-background scattering when interrogating structures using scattering approaches, complicating the resolution of colloidal structures. In this study, to circumvent this problem, a modified in vitro digestion model employing lipase immobilised on polymer beads, which allows for separation of the lipid digestion components during lipolysis, was investigated. Titration of the fatty acids released during digestion of medium chain triglycerides using pancreatin compared with immobilised lipase, combined with HPLC was used to follow the digestion, and small-angle X-ray scattering was used to determine colloidal structure formation. Digestion of medium chain triglycerides at the same nominal activity revealed that for the immobilised lipase, a longer digestion time was required to achieve the same extent of digestion. However, the same structural endpoint was observed, indicating that structure formation was not affected by the choice of lipase used. Lipolysis with immobilised lipase led to the reduction of parasitic scattering, resulting in clearer and more defined scattering from the structures generated by the lipolysis products.

PH-responsive micelles based on caprylic acid.

Free fatty acids play a vital role as fuel for cells and in lipid metabolism. During lipid digestion in the gastrointestinal tract, triglycerides are hydrolyzed, resulting in free fatty acid and monoglyceride amphiphilic products. These components, together with bile salts, are responsible for the transport of lipids and poorly water-soluble nutrients and xenobiotics from the intestine into the circulatory system of the body. In this study, we show that the self-assembly of digestion products from medium-chain triglycerides (tricaprylin) in combination with bile salt and phospholipid is highly pH-responsive. Individual building blocks of caprylic acid within the mixed colloidal structures are mapped using a combination of small-angle X-ray and neutron scattering combined with both solvent contrast variation and selective deuteration. Modeling of the scattering data shows transitions in the size and shape of the micelles in combination with a transfer of the caprylic acid from the core of the micelles to the shell or into the bulk water upon increasing pH. The results help to understand the process of lipid digestion with a focus on colloidal structure formation and transformation for the delivery of triglyceride lipids and other hydrophobic functional molecules.

Nanoparticle Organization in Sandwiched Polymer Brushes

The organization of nanoparticles inside grafted polymer layers is governed by the interplay of polymer-induced entropic interactions and the action of externally applied fields. Earlier work had shown that strong external forces can drive the formation of colloidal structures in polymer brushes. Here we show that external fields are not essential to obtain such colloidal patterns: we report Monte Carlo and molecular dynamics simulations that demonstrate that ordered structures can be achieved by compressing a "sandwich" of two grafted polymer layers, or by squeezing a coated nanotube, with nanoparticles in between. We show that the pattern formation can be efficiently controlled by the applied pressure, while the characteristic length-scale, that is, the typical width of the patterns, is sensitive to the length of the polymers. Based on the results of the simulations, we derive an approximate equation of state for nanosandwiches.

A model for the formation of colloidal structures in freight transportation: The case of hinterland terminals

An approach is presented to model the formation of spontaneously emerging associations of freight transport actors. Those agglomerations of logistics actors could be referred to as colloidal structures. The proposed approach combines insights from physics and economics. Typical logistics decisions are considered to be dynamic choices of consumers and providers resulting in temporally stable-market equilibria. The development of colloidal structures is driven by economies of scale on one hand and the preference for variety on the other hand. A case study with regards to intermodal terminals in Germany shows possible applications of the model for transport-policy analysis and planning.

The Synthesis of Mesoporous TiO2/SiO2/Fe2O3 Hybrid Particles Containing Micelle- Induced Macropores through an Aerosol Based Process

Mesoporous SiO(2)/TiO(2)/Fe(2)O(3) particles containing macropores of about 50 nm in diameter have been prepared by an aerosol process using cetyltrimethylammonium bromide (CTAB) as a templating agent. In contrast to the traditional templating effect of CTAB to form ordered mesoporous silicas, the morphology here is vastly different due to the presence of precursor iron salts. The particles have mesoporosity templated by CTAB but additionally have large voids leading to a combined macroporous and mesoporous structure. The morphology is explained through the formation of colloidal structures containing species such as CTA(+)X(-1)Fe(3+) colloids in the aerosol droplets, indicating of a salt bridging effect. This dual porosity has applied implications, as the macropores provide easy entry to the particle interior in potentially diffusion limited situations. Furthermore, the particles encapsulate Fe(2)O(3) and contain TiO(2) leading to the dual functional properties of magnetic response and photocatalytic activity.

Critical properties of binary liquid mixtures at different temperature modes

The coexistence curves (CC) of two binary mixtures, methanol-heptane (M-H) and perfluorodekaline-heptan (PFD-H), are measured for two temperature modes, namely heating and cooling. Distinctions in the behavior of the two systems in different temperature modes are revealed. For the M-H system this is likely to be attributed to the effects of surface processes and for the PFD-H systems, to the formation of colloidal structures. An additional signal related to the contribution of a meniscal layer is found and measured.