Bicontinuous Nature Research Articles

Synthesis and applications of polymer cubosomes and hexosomes

AbstractThe synthesis and use of polymer cubosomes have received significant attention in recent years. Polymer cubosomes are highly stable colloidal particles with triply periodic minimal surface. Inherently, polymer cubosomes have several advantages over other nanostructures like micelles and vesicles as they are quite uniform and porous structures. Due to the large specific surface area of the interior and bicontinuous nature, they have the capacity to load significant amounts of hydrophobic and hydrophilic substances. Additionally, their properties make them suitable for use as nanotemplates, catalyst supports, and nanovehicles for the separation and regulated release of biomolecules. Regarding their synthesis, block copolymers that may form cubosomes are still few in number, in part because different block copolymers require various self‐assembly conditions. In order to create polymer cubosomes, five different self‐assembly techniques have been reported, including the co‐solvent method, flash nanoprecipitation, evaporation‐induced self‐assembly, solvent‐diffusion‐evaporation‐mediated self‐assembly, and polymerization‐induced self‐assembly. This review article describes various synthetic techniques for creating polymer cubosomes and goes into further depth on recent uses for polymer cubosomes. It is anticipated that this article may offer some helpful guidance to researchers interested in the different applications of polymer cubosomes.

From Order to Disorder: Computational Design of Triblock Amphiphiles with 1 nm Domains.

Using molecular dynamics simulations and transferable force fields, we designed a series of symmetric triblock amphiphiles (or high-χ block oligomers) comprising incompatible sugar-based (A) and hydrocarbon (B) blocks that can self-assemble into ordered nanostructures with sub-1 nm domains and full domain pitches as small as 1.2 nm. Depending on the chain length and block sequence, the ordered morphologies include lamellae, perforated lamellae, and hexagonally perforated lamellae. The self-assembly of these amphiphiles bears some similarities, but also some differences, to those formed by symmetric triblock polymers. In lamellae formed by ABA amphiphiles, the fraction of B blocks "bridging" adjacent polar domains is nearly unity, much higher than that found for symmetric triblock polymers, and the bridging molecules adopt elongated conformations. In contrast, "looping" conformations are prevalent for A blocks of BAB amphiphiles. Above the order-disorder transition temperature, the disordered states are locally well-segregated yet the B blocks of ABA amphiphiles are significantly less stretched than in the lamellar phases. Analysis of both hydrogen-bonded and nonpolar clusters reveals the bicontinuous nature of these network phases. This simulation study furnishes detailed insights into structure-property relationships for mesophase formation on the 1 nm length scale that will aid further miniaturization for numerous applications.

Direct link between mechanical stability in gels and percolation of isostatic particles.

Colloidal gels have unique mechanical and transport properties that stem from their bicontinuous nature, in which a colloidal network is intertwined with a viscous solvent, and have found numerous applications in foods, cosmetics, and construction materials and for medical applications, such as cartilage replacements. So far, our understanding of the process of colloidal gelation is limited to long-time dynamical effects, where gelation is viewed as a phase separation process interrupted by the glass transition. However, this purely out-of-equilibrium thermodynamic picture does not address the emergence of mechanical stability. With confocal microscopy experiments, we reveal that mechanical metastability is reached only after isotropic percolation of locally isostatic environments, establishing a direct link between the load-bearing ability of gels and the isostaticity condition. Our work suggests an operative description of gels based on mechanical equilibrium and isostaticity, providing the physical basis for the stability and rheology of these materials.

Structural characterization of the [CnC1im][C4F9SO3] ionic liquid series: Alkyl versus perfluoroalkyl side chains

This work represents an essential step towards the understanding at a molecular level of the bulk structure of ionic liquids (ILs) that exhibit both an hydrogenated and a perfluorinated alkyl side chain. Molecular Dynamics (MD) simulations were performed along the 1-alkyl-3-methylimidazolium perfluorobutylsulfonate homologous series, [CnC1im][C4F9SO3] (2≤n≤12) in order to study in a systematic way the effect on the bulk structure of the change of the ratios between polar and nonpolar moieties and between hydrogenated and fluorinated moieties. The MD trajectories were used to calculate global and partial structure factors, S(q), of each IL. The low-q peaks obtained from the deconvolution of the total S(q) functions were assigned to characteristic lengths of the polar network and non-polar domains, also computed via the appropriate pair radial distribution functions. Finally, several aggregation analyses were performed in order to emphasize the bicontinuous nature of the liquids and its systematic and complex evolution along the series.

Cubosome particles of a novel Guerbet branched chain glycolipid

ABSTRACTCubic liquid crystalline nanoparticles (cubosomes) of bicontinuous nature with internal networks of water channels have received great interests in nanomedicine applications, particularly as potential vehicle for loading and release of therapeutic agents. These nanoparticles have been most commonly produced using monoolein and phytantriol. In this study, we explore the use of a Guerbet branched chain glycolipid, namely 2-hexyl-decyl-β-D glucopyranoside (β-Glc−OC10C6), as a new and alternative material for cubosomes production. The fully hydrated glycolipid assumes a reverse bicontinuous cubic liquid crystal phase of an Ia3d space group with lattice parameter of ca. 74 Å, as confirmed using a small-angle X-ray scattering. Dynamic light scattering and a conventional transmission electron microscopy were used to investigate the average size and morphology of the cubosomes. The effectiveness of Poloxamer 407 (stabiliser typically used in other cubosome systems against aggregations and particle coalescence) in providing steric stabilisation of the glycolipid cubosomes was assessed through visual assessment.

Experimental and numerical validation of the effective medium theory for the B-term band broadening in 1st and 2nd generation monolithic silica columns

Effective medium theory (EMT) expressions for the B-term band broadening in monolithic silica columns are presented at the whole-column as well as at the mesoporous skeleton level. Given the bi-continuous nature of the monolithic medium, regular as well as inverse formulations of the EMT-expressions have been established. The established expressions were validated by applying them to a set of experimental effective diffusion (Deff)-data obtained via peak parking on a number of 1st and 2nd generation monolithic silica columns, as well as to a set of numerical diffusion simulations in a simplified monolithic column representation (tetrahedral skeleton model) with different external porosities and internal diffusion coefficients. The numerically simulated diffusion data can be very closely represented over a very broad range of zone retention factors (up to k″=80) using the established EMT-expressions, especially when using the inverse variant. The expressions also allow representing the experimentally measured effective diffusion data very closely. The measured Deff/Dmol-values were found to decrease significantly with increasing retention factor, in general going from about Deff/Dmol=0.55 to 0.65 at low k″ (k″≅1.5–3.8) to Deff/Dmol=0.25 at very high k″ (k″≅40–80). These values are significantly larger than observed in fully-porous and core–shell particles. The intra-skeleton diffusion coefficient (Dpz) was typically found to be of the order of Dpz/Dmol=0.4, compared to Dpz/Dmol=0.2–0.35 observed in most particle-based columns. These higher Dpz/Dmol values are the cause of the higher Deff/Dmol values observed. In addition, it also appears that the higher internal diffusion is linked to the higher porosity of the mesoporous skeleton that has a relatively open structure with relatively wide pores. The observed (weak) relation between Dpz/Dmol and the zone retention factor appears to be in good agreement with that predicted when applying the regular variant of the EMT-expression directly to the mesoporous skeleton level.

Multi-Functionality of Macroporous TiO2 Spheres in Dye-Sensitized and Hybrid Heterojunction Solar Cells

Micron-sized macroporous TiO2 spheres (MAC-TiO2) were synthesized using a colloidal templating process inside emulsions, which were then coated on a nanocrystalline TiO2 light absorption film to prepare a bilayered photoanode for liquid-based dye-sensitized solar cells (DSSC) and hybrid heterojunction solid-state solar cells. MAC-TiO2 layers can enhance light scattering as well as absorption, because their pore size and periodicity are comparable to light wavelength for unique multiple scattering and a porous surface can load dye more. Moreover, due to the bicontinuous nature of macropores and TiO2 walls, electrolyte could be transported much faster in between the TiO2 spheres rather than within the small TiO2 nonporous architectures. Electron transport was also facilitated along the interconnected TiO2 walls. In DSSCs with these MAC-TiO2 scattering layers, efficiency was higher than conventional DSSCs incorporating a commercial scattering layer. The unique geometry of MAC-TiO2 results in strong improvements in light scattering and infiltration of hole-transporting materials, thereby the MAC-TiO2-based solid-state device showed comparatively higher efficiency than the device with conventional nanocrystalline TiO2.

Enhanced permeation, leaf retention, and plant protease inhibitor activity with bicontinuous microemulsions

Bicontinuous microemulsions (BCMEs) have excellent solubulizing properties along with low interfacial tension and aqueous content that can be controlled. In this work, water soluble plant protease inhibitor (PI), well characterized for its activity against insect pests, was incorporated into a BCME system and explored for permeation on hydrophobic leaf surfaces and protease inhibition activity. The bicontinuous nature of the microemulsion containing water:2-propanol:1-butanol (55:35:10w/w) was characterized using conductivity and self-diffusion coefficient measurements. The PI was soluble in the water-rich bicontinuous domains, stable in the microemulsions, and protease inhibition activity was retained for a prolonged duration. The microemulsions ensured greater wettability and a wider spread of the PI on hydrophobic leaf surfaces as revealed by contact angle measurements. Significantly, trypsin inhibition activity assays of the PI recovered from the leaves after delivery from the microemulsion indicated a significant increase in the PI retention on the leaf. This BCME enabled greater leaf permeation and retention of the PI can be attributed to a temporary disruption of the waxy leaf surface followed by self-repair without causing any long term damage to the plant.

Application of 3-D Hierarchically Porous Silver, Cobalt Oxide and Zinc Oxide Monoliths to Chromatographic Separations

ABSTRACTHierarchically porous silica monoliths were introduced into liquid phase chromatography at the beginning of the last decade. The high surface area, high void volume and bicontinuous nature of the porosity of the materials are significant advantages over existing chromatographic supports and have resulted in rapid acceptance of these materials into the chromatography market.We report here on the synthesis of 3-D porous silver, cobalt oxide and zinc oxide monoliths, their materials characterization, fabrication as liquid chromatographic columns and initial chromatographic characterization. The, as prepared, columns gave very low back pressure, consistent with the bicontinuous nature of the columns. Cobalt oxide and zinc oxide both demonstrated retention of a number of nitrogen heterocycles, providing the basis for molecular separation.

Lipid cubic phase as a membrane mimetic for integral membrane protein enzymes

The lipidic cubic mesophase has been used to crystallize important membrane proteins for high-resolution structure determination. To date, however, no integral membrane enzymes have yielded to this method, the in meso. For a crystal structure to be meaningful the target protein must be functional. Using the in meso method with a membrane enzyme requires that the protein is active in the mesophase that grows crystals. Because the cubic phase is sticky and viscous and is bicontinuous topologically, quantitatively assessing enzyme activity in meso is a challenge. Here, we describe a procedure for characterizing the catalytic properties of the integral membrane enzyme, diacylglycerol kinase, reconstituted into the bilayer of the lipidic cubic phase. The kinase activity of this elusive crystallographic target was monitored spectrophotometrically using a coupled assay in a high-throughput, 96-well plate format. In meso, the enzyme exhibits classic Michaelis-Menten kinetics and works with a range of lipid substrates. The fact that the enzyme and its lipid substrate and product remain confined to the porous mesophase while its water-soluble substrate and product are free to partition into the aqueous bathing solution suggests a general and convenient approach for characterizing membrane enzymes that function with lipids in a membrane-like environment. The distinctive rheology of the cubic phase means that a procedural step to physically separate substrate from product is not needed. Because of its open, bicontinuous nature, the cubic phase offers the added benefit that the protein is accessible for assay from both sides of the membrane.

Characterization of mixed DODAB/monoolein aggregates using Nile Red as a solvatochromic and anisotropy fluorescent probe

The aim of this study was to get a further knowledge of the interactions between lamellar and non-lamellar forming-phospholipids, as a tool to better understand the membrane dynamics and function. We have studied the behavior of aqueous mixtures of a cationic lipid (dioctadecyldimethylammonium bromide) and a neutral phospholipid (1-monoolein) in 10–150 μM total lipid concentration range. The effect of 1-monoolein on the physical properties (microviscosity, hydration and polarity) of the self-organized mixed aggregates was accessed by studying the steady-state fluorescence emission and anisotropy of the dye Nile Red. This information was combined with 90° Static Light Scattering assays in order to detect any structural variations in these vesicle systems. The results were interpreted by the coexistence of vesicular structures and other aggregates probably with a bicontinuous nature.

Gelled Polymerizable Microemulsions. 2. Microstructure

Using bicontinuous microemulsions as templates opens a new field for the design of novel structures and thus novel materials, but has significant challenges due to the very small composition and temperature windows in which microemulsions are bicontinuous. In previous work we had shown that we can take a ternary base system (water-n-dodecane--C 13/15E 5), add monomer and cross-linker ( N-isopropylacrylamide and N, N'-methylenebisacrylamide) to the water phase, and add a gelator (12-hydroxyoctadecanoic acid) to the oil phase while remaining in the one-phase region of the phase diagram. It was also possible to allow the gelator to form an organogel by changing the temperature such that we crossed the sol--gel line, which fell within the one-phase region. In this work, we show conclusively that addition of the monomers and the gelator does not affect the microemulsion microstructure and that, even in the gelled state, the polymerizable microemulsion is indeed bicontinuous. 1H NMR self-diffusion, conductivity, and small-angle neutron scattering measurements all confirm the bicontinuous nature of the gelled polymerizable microemulsion.

Characterisation of bicontinuous cubic liquid crystalline systems of phytantriol and water using cryo field emission scanning electron microscopy (cryo FESEM)

Cubosomes are a novel lipid particulate delivery system currently being investigated for drug delivery purposes. The present study investigates bicontinuous cubic liquid crystalline systems (bulk phase and cubosomes) formed by phytantriol and water using cryo field emission scanning electron microscopy (cryo FESEM). Previously cubosomes have been characterized by cryo transmission electron microscopy (cryo TEM) with small angle X-ray diffraction (SAXS) confirming the bicontinuous liquid crystalline type. Bulk cubic phase and cubosomes were prepared from phytantriol and Pluronic F127 and analysed using cryo FESEM and SAXS. The micrographs showed the cubic phase had a tortuous, bicontinuous nature with a non-intersecting network of water channels. The cubosomes also show the same underlying tortuous structure entirely consistent with that of the bulk cubic phase and closely resemble the mathematical description of cubosomes described using nodal surface representation. The structure of both systems was confirmed using SAXS as a bicontinuous cubic liquid crystalline phase with Pn3 m geometry. Cryo FESEM provides valuable insights into the morphological features of bicontinuous cubic liquid crystalline systems. The unique details shown provide strength to support the nodal surface representation of bicontinuous cubic liquid crystalline systems. Cryo FESEM provides a new technique to complement cryo TEM and SAXS for investigating their structure and function.

A new cationic surfactant N,N′-dimethyl-N-acryloyloxyundecyl piperazinium bromide and its pH-sensitive gels by microemulsion polymerisation

A piperazine-based cationic surfactant, N,N′-dimethyl-N-acryloyloxyundecyl piperazinium bromide (DAOUPB) was synthesised by a two-step procedure. The monomer was polymerised in two new microemulsion systems: (i) DAOUPB/water/methyl methacrylate (MMA):hydroxyethylmethacrylate (HEMA) and (ii) DAOUPB/water/acrylonitrile with ethyleneglycol dimethacrylate (EGDMA) as the crosslinking agent. Transparent solid polymeric materials were obtained by photo-initiated polymerisation of some of these microemulsion compositions. Most of the bicontinuous microemulsions investigated gelled within 10 min resulting in transparent solid polymers. The electron micrographs of the polymers obtained from microemulsion compositions containing MMA:HEMA did not show any micropores, while those obtained using acrylonitrile revealed the existence of open-cell type micropores and also of the bicontinuous nature of the system. The width of the bicontinuous structure (micropores) was about 33 nm in the dry state, with long and winding channels of random distribution. The swelling of the gels was highly sensitive to pH.

An Explicit Form of the Equation of Motion of the Interface in Bicontinuous Phases

The explicit form of the interface equation of motion derived assuming a minimal surface is extended to general bicontinuous interfaces that appear in the diffusion limited stage of the phase separation process of binary mixtures. The derivation is based on a formal solution of the equivalent simple layer for the Dirichlet problem of the Laplace equation with an arbitrary boundary surface. It is shown that the assumption of a minimal surface used in the previous linear theory is not necessary, but its bicontinuous nature is the essential condition required for us to rederive the explicit form of the simple layer. The de- rived curvature flow equation has a phenomenological cut-off length, i.e., an `electro-static' screening length. That is re- lated to the well-known scaling length characterizing the spatial pattern size of a homogeneously growing bicontinuous phase. The corresponding equation of the level function in this scheme is given in a one-parameter form also.

Effect of Adding Isopropyl Myristate to Microemulsions Based on Soybean Phosphatidylcholine and Triglycerides

The effect on the phase behavior and microstructure of pharmaceutically interesting microemulsions which is produced by adding isopropyl myristate (IPM) to the systems is described. The microemulsions are based on water, 1-propanol, soybean phosphatidylcholine (SbPC), and two different triglycerides; a medium-chain triglyceride (C8−C10) and a long-chain triglyceride (soybean oil). When IPM was added to the triglyceride oil phase, the spontaneous curvature of the surfactant film decreased and the flexibility of the surfactant monolayer increased. The change in spontaneous curvature was manifested by a gradual change in the microstructure of the microemulsion, as revealed by NMR self-diffusion data, from an oil-in-water type of structure at low concentrations of IPM to an oil continuous structure at higher IPM concentrations. At intermediate IPM concentrations, the microstructure was found to be of a bicontinuous nature. By optimizing the amount of IPM and the 1-propanol concentration, one-phase microemulsions containing equal amounts of water and oil can be obtained at lower surfactant concentrations and lower 1-propanol concentrations, compared with those for a system with only the triglyceride as the nonpolar phase.

Triglyceride-Based Microemulsion for Intravenous Administration of Sparingly Soluble Substances

□ A pharmaceutically acceptable microemulsion system composed of a medium-chain triglyceride (MCT), soybean phosphatidylcholine and poly(ethylene glycol)(660)-12-hydroxystearate (12-HSA-EO15) as amphiphiles, and poly(ethylene glycol) 400 (PEG 400) and ethanol as cosolvents is presented and characterized in terms of phase behavior, microstructure, solubilization capacity and in vivo effects after intravenous administration to conscious rats. At a total concentration of 11.9 wt % of soybean phosphatidylcholine and 12-HSA-EO15, a microemulsion region was formed over a wide range of α, where α is the weight fraction of MCT/(MCT+water+PEG 400+ethanol). The microstructure of the microemulsion was of a bicontinuous nature even at high oil concentrations. The mean droplet diameter of the oil-in-water emulsion formed after dilution of microemulsions prepared at different α within the one-phase region was between 60 and 200nm. It was concluded that it is possible to administer up to 0.5mL/kg of the microemulsion (α=0.5) without producing any significant effect on acid–base balance, blood gases, plasma electrolytes, mean arterial blood pressure (MAP), heart rate (HR), and PQ time (the time between depolarization of atrium and chamber). At a dose of 1.5mL/kg, a temporary increase in MAP, a decrease in HR, and a prolongation of the PQ time were observed.

Microporous Polymeric Materials from Polymerization of Zwitterionic Microemulsions

A new microemulsion system consisting of a polymerizable zwitterionic surfactant of (((acryloyloxy)undecyl)dimethylammonio)acetate (AUDMAA), methyl methacrylate (MMA), water with or without a cross-linking agent of ethylene glycol dimethacrylate (EGDMA) was investigated. Transparent solid polymeric materials can be produced by photoinitiated polymerization of some of these microemulsion compositions. Microemulsions with higher concentrations of EGDMA (>4%) or MMA (>50%) produced only turbid polymeric materials. However, it required a minimum of about 25% AUDMAA for producing a transparent polymeric material. Most of the bicontinuous microemulsions investigated could be gelled within 10 min and transparent solid polymers were finally obtained. Electron micrographs of these transparent polymers reveal the existence of not only the open-cell type microstructures but also the bicontinuous nature. The widths of the bicontinuous structures were about 50-70 nm, their lengths were long and winding and they appear to be randomly distributed. The microporous structures of these transparent polymeric materials seem to be related to the microstructures of the precursor bicontinuous-microemulsions. Perhaps, this is the first report to show the bicontinuous structures of microporous polymeric materials prepared by microemulsion polymerization.