Liquid Crystalline Hexagonal Phase Research Articles

Liquid crystalline inverted lipid phases encapsulating siRNA enhance lipid nanoparticle mediated transfection

Efficient cytosolic delivery of RNA molecules remains a formidable barrier for RNA therapeutic strategies. Lipid nanoparticles (LNPs) serve as state-of-the-art carriers that can deliver RNA molecules intracellularly, as exemplified by the recent implementation of several vaccines against SARS-CoV-2. Using a bottom-up rational design approach, we assemble LNPs that contain programmable lipid phases encapsulating small interfering RNA (siRNA). A combination of cryogenic transmission electron microscopy, cryogenic electron tomography and small-angle X-ray scattering reveals that we can form inverse hexagonal structures, which are present in a liquid crystalline nature within the LNP core. Comparison with lamellar LNPs reveals that the presence of inverse hexagonal phases enhances the intracellular silencing efficiency over lamellar structures. We then demonstrate that lamellar LNPs exhibit an in situ transition from a lamellar to inverse hexagonal phase upon interaction with anionic membranes, whereas LNPs containing pre-programmed liquid crystalline hexagonal phases bypass this transition for a more efficient one-step delivery mechanism, explaining the increased silencing effect. This rational design of LNPs with defined lipid structures aids in the understanding of the nano-bio interface and adds substantial value for LNP design, optimization and use.

PH-Dependent Self-Assembly of Human Neuropeptide Hormone GnRH into Functional Amyloid Nanofibrils and Hexagonal Phases.

Gonadotropin-releasing hormone (GnRH) is a short human neuropeptide involved in the regulation of sex hormones. We report that GnRH self-assembles into reversible β-sheet-based nanofibrils, with pH-dependent kinetics. At high concentrations, these nanostructures form arrays arranged in liquid crystalline hexagonal phases. Histidine deprotonation with increasing pH can mediate the formation of β-sheet-based precipitates. Our results are relevant to functional amyloids in general, to the intracellular storage process of GnRH within secretory granules, and to peptide hormone drug delivery.

Hydration properties of N-(α-hydroxyacyl)-sphingosine: X-ray powder diffraction and FT–Raman spectroscopic studies

The thermotropic properties of N-(α-hydroxyacyl)-sphingosine (CER[AS]) in dry and hydrated state were studied by means of X-ray powder diffraction and FT–Raman spectroscopy. The polymorphic states of the CER[AS]/water mixture (lamellar crystalline, lamellar hexagonal gel, liquid crystalline) depend on the thermal pre-treatment of the sample. Only by heating the CER[AS]/water mixture above the melting chain transition can the system be hydrated. At room temperature, both dry and hydrated states form lamellar structures, which differ in their repeat distance and packing of hydrocarbon chains. Above the melting chain transition, hydrated CER[AS] forms a liquid crystalline hexagonal phase, whereas anhydrous CER[AS] forms an isotropic liquid phase. The various phases of hydrated CER[AS] are distinguished on the basis of the corresponding Raman spectra.

Electrochemical characterization of a templated insulating polymer-modified electrode.

The controllable permselective behavior oftemplated poly(1,2-diaminobenzene)-modified electrodes is illustrated. The electrochemical behavior of polymer films prepared from several media, conventional aqueous solution, liquid crystalline micellar solution, and liquid crystalline hexagonal phase solution, were compared using several cationic and anionic redox probes. Films deposited from the hexagonal liquid crystalline phase were shown to be ion selective, allowing positively charged ions through to react at the electrode surface while excluding negatively charged ions. This permselective behavior was unique to the hexagonally templated films and was not exhibited by films deposited from either the conventional aqueous or the micellar media (which were completely blocking to both types of ion). In addition, it was shown that by altering the ionic strength of the background electrolyte control over the charge selective behavior of the hexagonally templated films was possible.

Fast and Easy Flow-Alignment Technique of Lyotropic Liquid-Crystalline Hexagonal Phases of Block Copolymers and Surfactants

Fast and Easy Flow-Alignment Technique of Lyotropic Liquid-Crystalline Hexagonal Phases of Block Copolymers and Surfactants

An X-ray scattering study of flow-aligned samples of a lyotropic liquid-crystalline hexagonal phase

Large flow-aligned samples of the hexagonal mesophase of the (sodium dodecylsulfate, pentanol, water) ternary system were produced by merely sucking the material into flat glass capillaries. These samples were examined by polarized light microscopy and X-ray scattering. In the plane of the hexagonal lattice, the “\(\)-mosaic” is only \(\) because the dense (10) hexagonal planes lie parallel to the flat glass plates of the capillaries. In contrast, the “\(\)-mosaic” of the C6 axis reaches 5-10\(\) because the samples undergo a thermomechanical instability of the columns already investigated by Oswald et al. in detail on the (C12EO6, H2O) system. Anisotropic thermal diffuse scattering is observed around the Bragg peaks and its description in the frame of an elastic continuum model provides estimates of the elastic constants. On heating the samples, we observed a clear splitting of four of the (10) hexagonal lattice reflections. This splitting is the defining signature of the thermomechanical instability by which the columns form zig-zags. The fact that two of the (10) reflections are not affected by the instability demonstrates that it is confined to the plane of the capillary. The influence of temperature on the thermomechanical instability was also studied in detail.

Phase diagram of tyloxapol and water — II

The phase diagram of mixtures of tyloxapol, a nonionic liquid polymer of the alkyl aryl polyether alcohol type, and water and the corresponding liquid crystalline phases have been investigated by X-ray scattering. Below 35 wt% tyloxapol micellar solutions are formed. At 3 wt% they contain spherical micelles with a diameter around 7 nm. Increasing concentrations give rise to interparticle interactions that are clearly observable above 10 wt%. Complementary viscosity measurements indicate a pronounced hydration of the polyoxyethylene chains. From 37.5 to 65 wt% there is a lyotropic liquid crystalline hexagonal phase (middle phase, M 1 phase). Its lattice parameter increases nearly linearly with water concentration but is almost independent of temperature. There are no transitions of the hexagonal phases to thermotropic liquid crystalline phases at temperatures between 20 and 65°C. At 65°C all systems exhibit two broad diffuse reflections with a spacing ratio of 1: 1 2 . At all concentrations, samples heated to 65°C and cooled to room temperature return to the hexagonal phase. The X-ray data confirm the existence of a cubic phase in a narrow concentration range around 70 wt% below 30°C. Its three-dimensional structure, however, could not be determined from the eight reflections in the scattering pattern. Retransformation of the cubic phase from the melt is highly retarded. On cooling, the cubic phase which is closest to the hexagonal phase at 20°C forms a metastable hexagonal intermediate phase with a small lattice parameter. The melts of cubic phases which exist in the vicinity of the lamellar phase region form an intermediate lamellar phase. Between 74 and 80 wt% at room temperature there is a liquid crystalline lamellar phase. The reflections of the thermally unstressed samples are weak compared with the sharp reflections observed after cooling of molten samples. The melts of all three liquid crystalline phases are viscous liquids. Their scattering patterns display two broad maxima with spacings progressively decreasing from 5.3 to 4.6 nm and from 2.7 to 2.4 nm as the concentration increases from 37.5 to 77.5 wt%. No liquid crystalline phases were observed for the binary mixtures containing more than 80 wt% but these highly viscous liquids display a broad maximum around 4.2 nm.

Phase diagram of tyioxapol and water — I

Tyloxapol, a nonionic liquid polymer of the alkyi aryl polyether alcohol type, described as freely soluble in water, is widely used in pharmacy. At room temperature and above, tyloxapol does not dissolve immediately in water but forms liquid crystalline structures in the contact zone with water resulting among others in the slow formation of aqueous one-phase systems. Macroscopically isotropic aqueous systems with a concentration-dependent viscosity are formed below 35 wt% tyloxapol. Around 35 wt% there is a narrow two-phase coexistence region. From 37.5 to 65 wt% textures of lyotropic liquid crystalline hexagonal phases are observed in the polarizing microscope. Solubilization tests indicate a hexagonal phase. This phase exists in a broad concentration and temperature range as derived from hot-stage polarizing microscopy and differential scanning calorimetry. The hexagonal phase exhibits the highest transition temperature (59°C) and the highest transition heats (0.5 J/g) around 50 wt%. Transmission electron microscopy (TEM) observations indicate a supramolecular arrangement consisting of parallel cylinders of non-uniform length resulting in two-dimensional order. In a narrow concentration range around 70 wt% and below 30°C, there is a stiff lyotropic liquid crystalline cubic phase with a transition heat of 1.3 J/g. Between 74 and 80 wt% at room temperature there is a liquid crystalline lamellar phase with low viscosity exhibiting no measurable transition heats. TEM observations indicate a supramolecular arrangement consisting of extended stacked lamellae exhibiting only one-dimensional order. The retransformation of the cubic phase from the melt is highly retarded. In contrast, the liquid crystalline hexagonal phase and lamellar phase are immediately formed on cooling of the melts to room temperature. Above 80 wt% the systems represent crystal dispersions.

Characterization of Mesoscopic Structures from Polymerizable Amphiphiles: The Water‐SSPOM System

AbstractSolutions of sodiumsulfopropyloctadecylmaleate (SSPOM) and water form ordered lamellar structures. Remarkable is that the structures form below the Krafft discontinuity indicating a frozen state of the hydrocarbon chains. Phase behaviour and microstructure were characterized using optical microscopy, differential scanning calorimetry (DSC), electrical conductivity, backscattering of light, small‐angle X‐ray scattering (SAXS) and freeze fracture electron microscopy (FFEM). We find a highly swollen lamellar structure displaying iridescent colours when illuminated with white light. The repeat distance of the bilayer membranes is estimated by light and X‐ray scattering and shows a non‐linear dependence on inverse surfactant concentration. Above the chain melting temperature near 37°C the liquid crystalline hexagonal phase (Ha) is observed.