Structure Of Lyotropic Liquid Crystals Research Articles

Cell Adhesion Motif-Functionalized Lipopeptides: Nanostructure and Selective Myoblast Cytocompatibility

The conformation and self-assembly of four lipopeptides, peptide amphiphiles comprising peptides conjugated to lipid chains, in aqueous solution have been examined. The peptide sequence in all four lipopeptides contains the integrin cell adhesion RGDS motif, and the cytocompatibility of the lipopeptides is also analyzed. Lipopeptides have either tetradecyl (C14, myristyl) or hexadecyl (C16, palmitoyl) lipid chains and peptide sequence WGGRGDS or GGGRGDS, that is, with either a tryptophan-containing WGG or triglycine GGG tripeptide spacer between the bioactive peptide motif and the alkyl chain. All four lipopeptides self-assemble above a critical aggregation concentration (CAC), determined through several comparative methods using circular dichroism (CD) and fluorescence. Spectroscopic methods [CD and Fourier transform infrared (FTIR) spectroscopy] show the presence of β-sheet structures, consistent with the extended nanotape, helical ribbon, and nanotube structures observed by cryogenic transmission electron microscopy (cryo-TEM). The high-quality cryo-TEM images clearly show the coexistence of helically twisted ribbon and nanotube structures for C14-WGGRGDS, which highlight the mechanism of nanotube formation by the closure of the ribbons. Small-angle X-ray scattering shows that the nanotapes comprise highly interdigitated peptide bilayers, which are also present in the walls of the nanotubes. Hydrogel formation was observed at sufficiently high concentrations or could be induced by a heat/cool protocol at lower concentrations. Birefringence due to nematic phase formation was observed for several of the lipopeptides, along with spontaneous flow alignment of the lyotropic liquid crystal structure in capillaries. Cell viability assays were performed using both L929 fibroblasts and C2C12 myoblasts to examine the potential uses of the lipopeptides in tissue engineering, with a specific focus on application to cultured (lab-grown) meat, based on myoblast cytocompatibility. Indeed, significantly higher cytocompatibility of myoblasts was observed for all four lipopeptides compared to that for fibroblasts, in particular at a lipopeptide concentration below the CAC. Cytocompatibility could also be improved using hydrogels as cell supports for fibroblasts or myoblasts. Our work highlights that precision control of peptide sequences using bulky aromatic residues within "linker sequences" along with alkyl chain selection can be used to tune the self-assembled nanostructure. In addition, the RGDS-based lipopeptides show promise as materials for tissue engineering, especially those of muscle precursor cells.

Light-Responsive Molecular Release from Cubosomes Using Swell-Squeeze Lattice Control.

Stimuli-responsive materials are crucial to advance controlled delivery systems for drugs and catalysts. Lyotropic liquid crystals (LLCs) have well-defined internal structures suitable to entrap small molecules and can be broken up into low-viscosity dispersions, aiding their application as delivery systems. In this work, we demonstrate the first example of light-responsive cubic LLC dispersions, or cubosomes, using photoswitchable amphiphiles to enable external control over the LLC structure and subsequent on-demand release of entrapped guest molecules. Azobenzene photosurfactants (AzoPS), containing a neutral tetraethylene glycol head group and azobenzene-alkyl tail, are combined (from 10-30 wt %) into monoolein-water systems to create LLC phases. Homogenization of the bulk LLC forms dispersions of particles, ∼200 nm in diameter with internal bicontinuous primitive cubic phases, as seen using small-angle X-ray scattering and cryo-transmission electron microscopy. Notably, increasing the AzoPS concentration leads to swelling of the cubic lattice, offering a method to tune the internal nanoscale structure. Upon UV irradiation, AzoPS within the cubosomes isomerizes within seconds, which in turn leads to squeezing of the cubic lattice and a decrease in the lattice parameter. This squeeze mechanism was successfully harnessed to enable phototriggerable release of trapped Nile Red guest molecules from the cubosome structure in minutes. The ability to control the internal structure of LLC dispersions using light, and the dramatic effect this has on the retention of entrapped molecules, suggests that these systems may have huge potential for the next-generation of nanodelivery.

Investigation into poloxamer 188‐based cubosomes as a polymeric carrier for poor water‐soluble actives

AbstractCubosomes and other lyotropic liquid crystal (LLC) phases are of great interest in many fields due to their potential as delivery systems. This study prepared poloxamer 188 (Pluronic® F68 [F68]) based cubosomes utilizing a low energy method and reports LLC structure stability, rheological behavior and carrier properties of the formed cubosomes. Mixtures of F68 and water were investigated and showed a concentration dependent viscoelastic behavior, ranging from a viscous liquid (30% F68) to hard gels (70% F68). Small‐angle X‐ray scattering showed cubosomes (Im3m) were present at F68 concentrations between 45% and 60%. Cubosomes fabricated from 50% F68 and 50% water were selected as the best composition and gave stable cubic structures for at least 10 months without additional stabilizing agent. To assess the use with poor water‐soluble molecules, artocarpin (AR) was added to the F68‐based cubosome. The developed cubosome possessed enhanced AR solubility due to the high affinity to the hydrophobic regions present in the cubic formation. Furthermore, an in vitro permeation study showed faster permeation rates of the developed cubosomes when compared to a cream‐based formulation. Collectively, these findings demonstrate that the F68‐based cubosomes represent a promising low‐cost active carrier for enhancing the solubility and permeability of low water‐soluble molecules.

Dember photovoltaic effect as method for structural characterization of phospholipidic membranes

Dember photovoltaic effect (Dember effect) was used to study permeability of a thin layer of lyotropic liquid crystal (dipalmitoylphosphatidylcholine) at various temperatures. By photo dissociation of a photosensitive ionic dye dissolved in a lyotropic liquid crystal, an inhomogeneous distribution of charge carriers was induced in a thin liquid crystal layer. The diffusion relaxation of these charge distributions depends on the structure of lyotropic liquid crystal and show up itself in the temperature dependence of pulsed photoelectric response. The data obtained are in a good agreement with the results of dielectric measurements. In perspective, above method can be applied to examine permeability of natural and synthetic lipid vesicles (cells, exosomes, liposomes and other vesicles) relevant in medicine and to characterize the structural phase transitions in lipid membranes when modified by molecules of interest (e.g. cholesterol in liposomes to increase rigidity and stability).

Temperature-sensitive lyotropic liquid crystals as systems for transdermal drug delivery

The purpose of this study was to develop temperature-sensitive lyotropic liquid crystals (LLC) for transdermal drug delivery systems. The hexagonal and cubic LLC samples were constructed in the polyoxyethylene (20) sorbitan monooleate (Tween 80)/PEG-60 hydrogenated castor oil (RH 60)/Ethyl oleate (EtOL)/water (H2O) system and characterized by Small Angle X-ray Scattering (SAXS), low field nuclear magnetic resonance (LF-NMR) and rheology. Additionally, its skin permeation behavior in vitro and cell-stimulating studies were investigated as well. The LLC system exhibited temperature sensitivity. Under the influence of temperature, the structure of LLC collapsed and was transformed into micellar solution. While, sample S3 (water content was 35 wt%.) was transformed from cubic LLC to hexagonal LLC then to micellar solution as temperature increased. The compositions and the introduction of paeonol both can influence the structure of LLC, and were used to adjust the phase transition temperature to close to the human body temperature. In vitro transdermal experiments showed that the release behavior of paeonol-loaded LLC was obviously temperature-sensitive and controlled by concentration diffusion. In vitro cell-stimulating studies displayed that LLC samples exhibited no obvious toxicity. The above results indicated that the temperature-sensitive LLC had potential to be applied as a transdermal drug delivery system.

Enhanced β-carotene encapsulation and protection in self-assembled lyotropic liquid crystal structures

The aim of this study was to form liquid crystalline structures for retaining and protecting β-carotene (β-c). Tween 40-Span 20 (TxSy) were blended for obtaining target hydrophilic-lipophilic balance (HLB) values ranging from 9 to 15. TxSy were mixed with canola oil (O) as carrier and water (W) as solvent and incubated for 10 days at 37 °C. The formation of lyotropic liquid crystals (LLC) was visually monitored. Pseudo-ternary phase diagrams were constructed to identify the region of LLC formation, which occurred only at HLB values of 11 and 12, the formation region being significantly larger in the former case. The experiments at HLB = 11 were repeated but substituting 0.7% of O by β-carotene (β-c) to produce LLC loaded with β-c (LLC β-c). Finally, LLC β-c were stored in darkness at 25 °C during five weeks. Best LLC β-c yield occurred for an O+β-c:TxSy:W ratio of 40:40:20 (p < 0.05), but the lowest degradation of β-c (17.26%) happened for an O+β-c:TxSy:W ratio of 36:54:10 (p < 0.05). This work provides a procedure for obtaining LLC systems for efficient protection, retention and/or release of nutraceuticals or bioactive compounds such as vitamins, antioxidants and smell substances, which may be used for developing novel food products with desired properties.

Formation of ion gels by polymerization of block copolymer/ionic liquid/oil mesophases.

In this study, we introduce a new method of developing ion gels through polymerization of lyotropic liquid crystal (LLC) templates of monomer (styrene), cross-linker (divinylbenzene), ionic liquid (1-ethyl-3-methylimidazolium tetrafluoroborate), and amphiphilic block copolymers (Pluronic F127). The polymerization of the oil phase boosts the mechanical properties of the ion-conducting electrolytes. We discuss the effect of tortuosity induced by crystalline domains and LLC structure on the conductivity of ion gels. The ion transport in polymerized LLCs (polyLLCs) can be controlled by changing the composition of the mesophases. Increasing the block copolymer concentration enhances the crystallinity of PEO blocks in the conductive domains, which slows down the dynamics of PEO chain and ion transport. We show that by adjusting the composition of LLC mesophases, the mechanical strength of ion gels can be increased one order of magnitude without compromising the ionic conductivity. The polyLLCs with 45/25/30 wt% (block copolymer/IL/oil) composition has storage modulus and ionic conductivity higher than 1 MPa and 3 mS cm-1 at 70 °C, respectively. The results suggest that LLC templating is a promising method to develop highly conductive ion gels, which provides advantages in terms of variety and processing.

Formulating and Retaining the Structure of Polymerized Surfactant Phases Using a Microemulsion Curvature Framework.

Nanostructured polymers contain features smaller than 100 nm that are useful in a wide range of areas, including photonics, biomedical materials, and environmental applications. Out of the myriad of nanostructured polymers, surfactant-templated polymers are versatile because of their ability to have tunable domain sizes, structure, and composition. This work addresses the gap between the formulation with industrial-grade polymerizable surfactants and the final structure of the polymer, using the hydrophilic-lipophilic difference (HLD) and net-average curvature (NAC) frameworks. HLD indicates the proximity of the formulation (surfactant and oil monomer selection, temperature, electrolyte concentration) to the phase inversion point, where HLD = 0. NAC uses the HLD to determine the curvature of the surfactant-oil-water interface, leading not only to the size and shape of micelles and bicontinuous isotropic (L3) systems but also to defining the most likely regions for lyotropic liquid crystal (LLC) existence and phase separation in ternary phase diagrams. Polymerizing LLC fluids produced nanostructured polymers with similar LLC structures that were highly swellable, but with low compressive strength. Polymerizing L3 fluids produced strong, but less water-swellable nanostructured polymers with a similar characteristic length to the parent L3 microemulsion. The relatively small scale of the parent LLC (∼6-8 nm) or L3 (∼3-4 nm) systems is consistent with the translucent nature of the polymers produced and the HLD-NAC predicted sizes.

Effect of 1-butyl-3-methylimidazolium chloride on the lyotropic liquid crystal structure and properties of TX-100/oleic acid/water system

The lyotropic liquid crystals (LLCs) of polyoxyethylene tert-octylphenyl ether (TX-100)/oleic acid/water systems formed before and after adding [BMim]Cl were characterized by polarized optical microscopy, small-angle X-ray scattering technique, and rheological and conductivity measurements. The structure of LLCs transformed gradually from hexagonal to lamellar with the increase in [BMim]Cl percentage. Interactions between molecules in the TX-100/oleic acid/water/[BMim]Cl LLC system were initially explored by Fourier transform infrared spectroscopy. These results inspired the use of imidazolium chlorides and oleic acid in LLC regulation. All the LLCs containing [BMim]Cl had high ionic conductivities, thereby demonstrating the potential of TX-100/oleic acid/water/[Bmim]Cl LLC system as an ion transport material with size-adjustable nanochannels.

Influence of Ionizing Radiation on the Structure of a Lyotropic Liquid Crystal

With the aid of the simultaneous diffraction of X-rays at large and small angles and the optical polarizing microscope, the influence of the gamma rays on the structure of lyotropic lamellar liquid crystals has been investigated. It is shown that the balance between the electrostatic repulsive and Van der Waals attractive forces changes in the lamella owing to the influence of these rays. This results in the changes of such parameters of the lamella structure, as its thickness, the partial area per one head of the phospholipid molecule, and the crystallization effect. As a result, the phospholipid bilayer is swollen and the microstresses arise.

On the Structure and Transdermal Profile of Liquid Crystals Based on Phytantriol.

There has been a growing concern in transdermal drug technology over the past several decades. As a novel transdermal delivery system, Lyotropic liquid crystals (LLC) still face challenges such as drug loading, limited drug permeation and instability of systems. LLC system is so sensitive that a very subtle change in composition may induce a phase transformation or conversion of spatial configuration, and result in a diverse percutaneous delivery subsequently. To find out the effects of hydrophilic and lipophilic components on the structure and transdermal properties of LLCs, hydrophilic sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) was chosen as a model drug and a skin permeation enhancer, respectively, several formulations were prepared and compared. The structure of LLC was evaluated by visual observation, Cross-polarizing light microscopy (CPLM) and Small angle X-ray diffraction (SAXS). The Franz diffusion cell was applied to investigate its skin penetration of SH across the rat skins. Fourier transform infrared spectroscopy (FTIR) was recorded to evaluate the intermolecular interaction between the LC samples and stratum corneum (SC). The results showed that a controlled transdermal process might be obtained by adjusting the ratios of different drugs or loading doses when LLCs with dual-components were applied.

Factors affecting the structure of lyotropic liquid crystals and the correlation between structure and drug diffusion.

Lyotropic liquid crystals (LLCs) formed by the self-assembly of amphiphilic molecules in a solvent (usually water) have attracted increasingly greater attention in the last few decades, especially the lamellar phase (Lα), the reversed bicontinuous cubic phase (Q2) and the reversed hexagonal phase (H2). Such phases offer promising prospects for encapsulation of a wide range of target molecules with various sizes and polarities owing to the unique internal structures. Also, different structures of mesophases can give rise to different diffusion coefficients. The bicontinuous cubic phase and the hexagonal phase have been demonstrated to control and sustain the release of active molecules. Furthermore, the structures are susceptible to many factors such as water content, temperature, pH, the presence of additives etc. Many researchers have been studying these influencing factors in order to accurately fabricate the desired phase. In this paper, we give a review of the characteristics of different structures of liquid crystalline phases, the influencing factors on the phase transition of liquid crystals and the relationship between structures of LLC and drug diffusion. We hope our review will provide some insights into how to manipulate in a controlled manner the rate of incorporating and transferring molecules by altering the structure of lyotropic mesophases.

Effects of a volatile solvent with low surface tension combining with the silica network reinforcement on retention of LLC structure in polymer matrix

Organic polymers with ordered nanostructures templated from lyotropic liquid crystals (LLC) have many potential applications in areas such as membranes, tissue engineering, and drug delivery. However, after removing the LLC templates, the high surface tension during vacuum or air drying will deform the structure to a great extent. This study investigates the structure retention in cross-linked poly(ethylene glycol) diacrylate polymer through reinforcement of a silica network and using a volatile solvent with low surface tension. The LLC templates were formed from non-ionic surfactant, Brij 56/water system. Silica network was obtained through a sol–gel method using TEOS as a silica precursor and hydrochloric acid as a catalyst. The LLC templates were removed and the samples were dried from this solvent using a mixed solvent n-hexane and ethanol (H–E solvent) with lower surface tension. Samples dried from H–E solvent preserved the structure template from LLC even with low TEOS loading due to the presence of a non-polar solvent that has little effect on silica reverse hydrolysis and lower surface tension. This indicates that drying the sample from a volatile solvent with low surface tension combining with the silica network reinforcement facilities the structure retention.

Influence of UV Radiation on Structure of Lyotropic Liquid Crystals

Molecular mechanisms of the impact of ultraviolet (UV) rays on biological systems can be divided into three categories: structural and functional changes of DNA, photoinactivation of proteins and structural damage of cell membranes. Though a large number of studies have explored the first two categories of UV ray impacts on biological systems and have proposed various feasible models for the pathways of these impacts, few studies have explored structural damage of cell membranes and the only proposed mechanisms for this UV impact is that of lipid, peroxide, and amino acid oxidation with the impact of various wave lengths of UV rays, A (400–320 nm), B (300–275 nm), and C (275–180 nm) being explained by these mechanisms. In the present work, we have studied the biological impact of UV rays on the phospholipid bilayer by using simultaneous small and large angle X-ray diffraction method.

Hexagonal closest-packed spheres liquid crystalline phases stabilised by strongly hydrated counterions

The sequence and structure of lyotropic liquid crystals formed in C12-C16 alkyltrimethylammonium surfactants with hydrolysable and multivalent phosphate (PO4(3-), HPO4(2-) and H2PO4(-)), oxalate (HC2O4(-) and C2O4(2-)), and carbonate (HCO3(-)/CO3(2-)) counterions were determined using a concentration gradient method coupled with polarising optical microscopy and small angle X-ray scattering. In addition to the discrete cubic (I1, space group Pm3n) and hexagonal (H1, p6m) phases, almost all of these surfactants also formed the (previously) rare hexagonally closest-packed spheres (HCPS, P63/mmc) phase at compositions between the Pm3n cubic and L1 micellar phases. This structure has not been previously observed in cationic surfactants, but is readily achieved by using strongly hydrated counterions to stabilise spherical micelles at high concentrations.

Retention of the original LLC structure in a cross-linked poly(ethylene glycol) diacrylate hydrogel with reinforcement from a silica network.

Cross-linked poly(ethylene glycol) diacrylate (PEGDA) hydrogels with uniformly controlled nanoporous structures templated from hexagonal lyotropic liquid crystals (LLC) represent separation membrane materials with potentially high permeability and selectivity due to their high pore density and narrow pore size distribution. However, retaining LLC templated nanostructures is a challenge as the polymer gels are not strong enough to sustain the surface tension during the drying process. In the current study, cross-linked PEGDA gels were reinforced with a silica network synthesized via an in situ sol-gel method, which assists in the retention of the hexagonal LLC structure. The silica precursor does not obstruct the formation of hexagonal phases. After surfactant removal and drying, these hexagonal structures in samples with a certain amount of tetraethoxysilane (TEOS) loading are well retained while the nanostructures are collapsed in samples without silica reinforcement, leading to the hypothesis that the reinforcement provided by the silica network stabilizes the LLC structure. The study examines the conditions necessary for a sufficient and well dispersed silica network in PEGDA gels that contributes to the retention of original LLC structures, which potentially enables broad applications of these gels as biomedical and membrane materials.

Improved stimuli-response and mechanical properties of nanostructured poly(N-isopropylacrylamide-co-dimethylsiloxane) hydrogels generated through photopolymerization in lyotropic liquid crystal templates

Temperature-sensitive poly(N-isopropylacrylamide) (PNIPAM) hydrogels are widely studied stimuli-responsive systems due to their significant volume changes at biologically relevant temperatures and a potential wide range of applications including drug delivery, cell cultures, chemical sensors, and desalination. The successful performance of PNIPAM gels often requires a rapid response rate with a significant degree of deswelling when heated above the lower critical solution temperature. However, it is often difficult to design PNIPAM hydrogels with appropriate mechanical strength for the gels to remain functional in a working environment. Herein, lyotropic liquid crystals (LLCs) are utilized to generate a hexagonal nanostructure in PNIPAM hydrogels in order to improve material properties and transport characteristics. Cross-linked methacrylated poly(dimethylsiloxane) (PDMS) was incorporated into PNIPAM gels at varying concentrations through photopolymerization in the hexagonal LLC phase in order to modulate mechanical properties. The hexagonal LLC nanostructure dramatically increases the hydrogel deswelling rate compared to traditional isotropic PNIPAM–PDMS hydrogels of the same chemical composition. Additionally, the ordered LLC structure allows for considerable incorporation of PDMS into the hydrogel without significantly decreasing the water content of the gels. Interestingly, the hexagonal nanostructured hydrogels exhibit similar compressive moduli compared to isotropic hydrogel controls despite having considerably higher water content. These results may be utilized to generate stimuli-sensitive hydrogels with an appropriate rate and degree of deswelling while maintaining necessary mechanical integrity of the gel for use in numerous biomedical and industrial applications.

Location of Phase Boundaries of Lyotropic Liquid Crystal Employing Positron Lifetime Spectroscopy and Electrical Conductivity Measurement

Different compositions of surfactant systems give rise to a rich variety of structures of aggregates. At higher concentrations of surfactant in water, the surfactant molecules aggregate to form lyotropic liquid crystals [1]. In the present work we have prepared two surfactant systems consisting of (i) 20% of cetyl-trimethyl-ammonium-bromide (CTAB) in water, and (ii) 30% of tetra-decyl-trimethyl-ammonium-bromide (TTAB) in water. Both the systems exhibit various lyotropic liquid crystal structures when an increasing amount of co-surfactant is added as third component [2, 3]. These liquid crystalline structures are very sensitive to the solution conditions such as co-surfactant concentration, temperature, ionic strength, counter ion polarizability etc. In this study, positron life time spectroscopy and conductivity measurement have been employed to locate various phases exhibited by the lyotropic liquid crystals. In addition to delineating various phase boundaries of the systems, positron annihilation technique has also yielded new findings.

The Study of Lyotropic Liquid Crystal Structure Using the Molecular Dynamics Simulation Method

We have performed a 500 ns Molecular Dynamics (MD) to study the lamellar phase of lyotropic liquid crystasl consisting of more or less hydrophobic lamellas. As more hydrophobic lamellas were used lamellas of biological origin, in this case, asymmetric human erythrocyte membrane and as less hydrophobic lamellas—planar micelles of sodium pentadecylsulfonate (SPDS), representing a commercial interest. Some important parameters have been obtained which characterize the dynamic structure of lyotropic liquid crystal's lamella. A good correspondence is established for the results of computer and physical experiments.

Structure retention in cross-linked poly(ethylene glycol) diacrylate hydrogel templated from a hexagonal lyotropic liquid crystal by controlling the surface tension

Retaining hexagonal lyotropic liquid crystal (LLC) structures in polymers after surfactant removal and drying is particularly challenging, as the surface tension existing during the drying processes tends to change the morphology. In this study, cross-linked poly(ethylene glycol) diacrylate (PEGDA) hydrogels were prepared in LLC hexagonal phases formed from a dodecyltrimethylammonium bromide (DTAB)/water system. The retention of the hexagonal LLC structures was examined by controlling the surface tension. Polarized light microscopy, X-ray diffraction and small angle X-ray scattering results indicate that the hexagonal LLC structure was successfully formed before polymerization and well retained after polymerization and after surfactant removal when the surface tension forces remained neutral. Controlling the surface tension during the drying process can retain the nanostructures templated from lyotropic liquid crystals which will result in the formation of materials with desired nanostructures.