Reverse Hexagonal Mesophases Research Articles

Heterogeneous micellar solubilization within lyotropic liquid crystals interfaces

The solubilization of sodium diclofenac (Na-DFC) in a glycerol monooleate-based emulsion triggers series of structural changes. Incorporation of Na-DFC, leads to formation of a reverse hexagonal mesophase between 2 and 5 wt% Na-DFC. Between 6 and 9 wt% Na-DFC, the hexagonal symmetry gradually transitions to a disordered lamellar mesophase. These structural shifts impact the system's storage modulus, structuring enthalpy, and structural diffusivity. Despite these transitions, the driving force for Na-DFC release remains consistent, leading to hypothesize that the interfacial structure remains unchanged during Na-DFC release.The nano-structural modifications imposed by the Na-DFC load and release were assessed by small-angle X-ray diffraction (SAXD), spin-probe electron paramagnetic resonance (EPR), and nuclear quadrupole resonance (NQR).The selective solubilization of Na-DFC was demonstrated by SAXD peak fittings, revealing an increase of hexagonally oriented rods at the expense of non-oriented micelles, rather than gradual micellar elongation. Computation of the EPR spectra also showcased the selective solubilization of Na-DFC at an enhanced free energy interface (γ), evidenced by step-wise variations in polarity, microviscosity, and order parameters. Additionally, NQR analysis highlighted a higher anisotropy for sodium compared to deuterium, linking the selective solubilization of Na-DFC to heterogeneous structural transformations. These findings underscore the heterogeneous nature of solubilization-release processes, driven by locally increased micellar free energy. Consequently, the loaded Na-DFC interfaces maintain a constant γ, ensuring a consistent release driving force despite the structural transitions affecting the matrix. The ability to selectively solubilize guest molecules may herald a new era in the utilization of selective molecular interfacial loading.

Structural transformations and phase transitions in hexagonal La-containing lyomesophases

Understanding and identification of phase equilibrium in self-assembling systems like lyotropic liquid crystals (LLCs) plays a key role in their further practical applications. In this study the phase transitions in LLCs based on С12ЕО10 nonionic surfactant, lanthanum nitrate hexahydrate, and water are reported. Polarized optical microscopy, X-ray powder diffraction, and fluorimetry were used to find correlations between system composition and structural changes. A new approach to identify a reverse hexagonal mesophase by the analysis of concentration dependencies of mesophase structural parameters was proposed. Data from these experiments were further compared with pyrene fluorescence studies to confirm the phase inversion. Based on complex analyses of experimental data an inversion of hexagonal mesophases via intermediate lamellar phase in the С12ЕО10(LaIII)/H2O system was found at the concentration ratio of 85/15 wt.%. The interpreted temperature-composition phase diagram was plotted. The regions of existence of direct hexagonal, intermediate mesophases and reverse hexagonal were found in the С12ЕО10(LaIII)/H2O system.

Progress and challenges of lyotropic liquid crystalline nanoparticles for innovative therapies

Since the late 20th century, we have witnessed a growing and substantial advance in nanomedicine, in part due to the development of multifunctional and multimodal nanoplatforms that have enabled improved efficacy, biocompatibility, and novel therapeutic applications. Non-lamellar liquid-crystalline nanoparticles, especially, reverse hexagonal and cubic bicontinuous mesophases, have gained the attention of the scientific-academic community due to their intriguing and functional characteristics, such as self-organization into two- and three-dimensional supramolecular structures, high symmetry, and ability to accommodate hydrophobic and hydrophilic small molecules, peptides, proteins, nucleic acids, and imaging agents. Furthermore, these particles can be easily modified with specific and/or bioresponsive molecules allowing targeting and improved therapeutic performance. In this contribution we provide an overview of advances in the design and architecture of LCNPs, strategies to overcome biological barriers and main findings about interactions with different types of interfaces. We highlight recent applications in topical, oral, pulmonary and intravenous drug delivery in preclinical in vivo studies. We discussed the current scenario and translational obstacles faced for clinical translation, as well as our perspectives.

Size-tunable silica nanowires prepared using reverse microemulsion-gel systems

Abstract Self-assembled hybrid gels were formed by adding amounts of tetraethyl orthosilicate (TEOS) dissolved in water to organic solutions of sodium bis(2-ethylhexyl) sulfosuccinate (Aerosol-OT, AOT). Two kinds of hybrid gels were prepared and discussed in this study. In the first, gels were prepared through chemical hydrolysis-condensation reactions of TEOS. The growth of a one-dimensional silica network in the confinement of the AOT reverse microemulsions led to gel formation. In the other, gels were prepared through reverse hexagonal mesophases due to high concentrations of AOT. Rheological studies demonstrated that the elastic modulus, G', is greater than the viscous modulus, G, at all frequencies, and G' did not depend upon the frequency in either system, implying they can be used as gels. The gels obtained through silica networks had smaller G' values and higher transformation strains than those gels prepared through AOT reverse hexagonal mesophases. Small-angle X-ray scattering (SAXS) results showed that both systems exhibited cylindrical structures with short-range order, and the radii of the cylinders were significantly influenced by the change of AOT, TEOS and water concentrations. Transmission electron microscopy (TEM) confirmed that silica nanowires were found in both gel systems after removing the AOT components. The length of the nanowires for the gels prepared through silica networks was larger than that for the gels prepared through AOT reverse hexagonal mesophases. This was because the silica grew into a one-dimensional network (axial direction) due to the confinement of the cylindrical structures.

Polymerization in soft nanoconfinement of lamellar and reverse hexagonal mesophases.

This work describes the kinetics of thermal polymerization in nanoconfined domains of lyotropic liquid crystal (LLC) templates by using chemorheological studies at different temperatures. We investigate lamellar and reverse hexagonal LLC phases with the same concentration of the monomeric phase. Results show that the mesophase structures remain intact during thermal polymerization with very slight changes in the domain size. The polymerization rate decreases in the nanoconfined structure compared to the bulk state due to the segregation effect, which increases the local monomer concentration and enhances the termination rate. Additionally, the polymerization rate is faster in the studied reverse hexagonal systems compared to the lamellar ones due to their lower degree of confinement. A higher degree of confinement also induces a lower monomer conversion. Differential scanning calorimetry confirms the obtained results from chemorheology.

Controlling insulin release from reverse hexagonal (HII) liquid crystalline mesophase by enzymatic lipolysis

In the present study we aimed to control insulin release from the reverse hexagonal (HII) mesophase using Thermomyces lanuginosa lipase (TLL) in the environment (outer TLL) or within the HII cylinders (inner TLL). Two insulin-loaded systems differing by the presence (or absence) of phosphatidylcholine (PC) were examined.In general, incorporation of PC into the HII interface (without TLL) increased insulin release, as a more cooperative system was formed.Addition of TLL to the systems’ environments resulted in lipolysis of the HII structure. In the absence of PC, the lipolysis was more dominant and led to a significant increase in insulin release (50% after 8h). However, the presence of PC stabilized the interface, hindering the lipolysis, and therefore no impact on the release profile was detected during the first 8h.Entrapment of TLL within the HII cylinders (with and without PC) drastically increased insulin release in both systems up to 100%. In the presence of PC insulin released faster and the structure was more stable.Consequently, the presence of lipases (inner or outer) both enhanced the destruction of the carrier, and provided sustained release of the entrapped insulin.

Progesterone solubilization within reverse hexagonal mesophase

The present work reports on the preparation and characterization of progesterone-loaded reverse hexagonal (HII) mesophase based on a glycerol monooleate (GMO)/tricaprylin (TAG)/water mixture for transdermal application.Several compositions into which progesterone was quantitatively solubilized were selected and used in the present study in order to evaluate the effect of the hormone on structural transitions and characteristics.A GMO/TAG of 90:1wt ratio with 20wt% water was found to form HII mesophases with relative high solubilization capacity of 4wt% progesterone and a shelf life of over one year. The structures were identified by cross-polarized light microscopy (CPLM). Structural confirmations were obtained from small-angle X-ray scattering (SAXS) measurements. The hormone is solubilized at the interface of the HII mesophase as confirmed by SAXS, rheology, FTIR, and DSC. The progesterone, which is loaded onto reverse hexagonal cylinders, leads to strengthening the hydrogen bonding and to better packing of the HII mesophase, suggesting that progesterone is a kosmotropic agent.The reverse hexagonal mesophase seems to be a promising carrier for solubilization of progesterone.

Structural properties and release of insulin-loaded reverse hexagonal (HII) liquid crystalline mesophase

Insulin loading into the HII mesophases was examined as a function of its concentration, with addition of glycerol as a cosolvent and with addition of phosphatidylcholine (PC) as a structural stabilizer. The structural properties, the molecular interactions, the viscoelastic properties, and the dynamic behavior were investigated by SAXS, ATR-FTIR, and rheological measurements. Insulin release was then monitored and analyzed. Insulin incorporation into the HII systems shrank the cylinders as it competed with the lipids in water-bonding. Insulin interrupted the interface while increasing τmax and creating a more solid-like response. Upon addition of PC, cooperative flow behavior was detected, which is probably the reason for increase in insulin cumulative release from 28% to 52% after 300 min. In the presence of glycerol, the system was less cooperative but insulin was more compactly folded, resulting in a slight improvement in insulin release (up to 6%). Addition of both PC and glycerol caused the maximum release (55%). The addition of additives into the HII system demonstrates how structural modifications can improve insulin release, and influence future design of encapsulated drug delivery systems.

Exploring the Phase Behavior of Monoolein/Oleic Acid/Water Systems for Enhanced Donezepil Administration for Alzheimer Disease Treatment

Donepezil is a drug usually administered by oral route for Alzheimer disease treatment, but several gastric side effects have been reported as diarrhea, nausea, and anorexia. We explored the phase behavior of lyotropic liquid crystalline (LLC) mesophases composed by monoolein/oleic acid/water for enhanced administration of donepezil. Polarized light microscopy suggested that these systems ranged from isotropic inverse micellar solutions (L2) to viscous and birefringent reverse hexagonal (HII) mesophases according to the amount of water in the ternary systems. Phase transition was observed from a L2 phase to HII mesophase after swelling studies, an interesting property to be explored as a precursor of LLC mesophases for mucosal administration that increases its viscosity in situ. Mucoadhesive properties of LLC mesophases were characterized using a texture analyzer indicating that these systems can have an increased residence time in the site of absorption. Donepezil-free base was incorporated in the evaluated formulations, and their in vitro release was controlled up to 24 h. The phase behavior of the systems demonstrated a great potential for enhanced donepezil administration once these mucoadhesive–controlled release formulations can incorporate the drug and prolong its release, possibly reducing its side effects.

Solvation Dynamics in Different Phases of the Lyotropic Liquid Crystalline System.

Reverse hexagonal (HII) liquid crystalline material based on glycerol monooleate (GMO) is considered as a potential carrier for drugs and other important biomolecules due to its thermotropic phase change and excellent morphology. In this work, the dynamics of encapsulated water, which plays important role in stabilization and formation of reverse hexagonal mesophase, has been investigated by time dependent Stokes shift method using Coumarin-343 as a solvation probe. The formation of the reverse hexagonal mesophase (HII) and transformation to the L2 phase have been monitored using small-angle X-ray scattering and polarized light microscopy experiments. REES studies suggest the existence of different polar regions in both HII and L2 systems. The solvation dynamics study inside the reverse hexagonal (HII) phase reveals the existence of two different types of water molecules exhibiting dynamics on a 120-900 ps time scale. The estimated diffusion coefficients of both types of water molecules obtained from the observed dynamics are in good agreement with the measured diffusion coefficient collected from the NMR study. The calculated activation energy is found to be 2.05 kcal/mol, which is associated with coupled rotational-translational water relaxation dynamics upon the transition from "bound" to "quasi-free" state. The observed ∼2 ns faster dynamics of the L2 phase compared to the HII phase may be associated with both the phase transformation as well as thermotropic effect on the relaxation process. Microviscosities calculated from time-resolved anisotropy studies infer that the interface is almost ∼22 times higher viscous than the central part of the cylinder. Overall, our results reveal the unique dynamical features of water inside the cylinder of reverse hexagonal and inverse micellar phases.

Reversed Hexagonal Lyotropic Liquid-Crystal and Open-Shell Glycodendrimers as Potential Vehicles for Sustained Release of Sodium Diclofenac

The effect of second, third, and fifth generations of poly(propylene imine) glycodendrimers-open maltose shell (PPI-Mal) on reverse hexagonal (HII) mesophase and on the release of sodium diclofenac (Na-DFC) drug was investigated. The HII mesophase comprised glycerol monooleate (GMO)/tricaprylin (TAG) in a weight ratio of 90/10 and 20 wt % water (+0.5 wt % PPI-Mal of each generation) without or with 0.25 wt % (Na-DFC). The microstructural characteristics of these systems were determined by small-angle X-ray scattering; attenuated total reflectance Fourier transform infrared was used to characterize the molecular level interactions and the location of the PPI-Mal. Third-and fifth-generation PPI-Mal, because of their maltose groups, interact mainly with the bulk water within the cylinders of the HII and strongly bind the water molecules, as manifested by the decrease in the lattice parameter and dehydration of the lipid headgroups. Co-solubilization of Na-DFC with the third and fifth generations caused competition of the two host compounds for water binding and induced relocation of the drug from the bulk water to the GMO-water interface. In vitro release of Na-DFC from the HII showed that the release process was faster in the systems with third- and fifth-generation PPI-Mal compared with the control and second-generation systems.

Reconstitution of OmpF membrane protein on bended lipid bilayers: perforated hexagonal mesophases

Membrane proteins have been reconstituted on lipid bilayers with zero mean-curvature (cubic phases or vesicles). Here we show that reconstitution of pore-forming membrane proteins can also occur on highly curved lipidic bilayers of reverse hexagonal mesophases, for which the mean-curvature is significantly different from zero. We further show that the membrane protein provides unique topological interconnectivities between the aqueous nanochannels, significantly enhancing mesophase transport properties.

Modulation of physical properties of reverse hexagonal mesophases: A dielectric spectroscopy study

The structural, dynamic, and kinetic aspects of the HII systems based on glycerol monooleate (GMO), phosphatidylcholine (PC), triacylglycerol (TAG), and water were investigated by dielectric spectroscopy in a frequency range of 10-2–106 Hz, and a temperature range of 290–320 K. Three distinct processes as well as a temperature-activated dc conductivity were detected and examined. These were assigned to the reorientation of the GMO polar heads, the tangential movement of counterions at the interface, the transport of TAGs through the lipids tails, and the ion mobility within the water cylinders.Upon addition of PC, the critical temperature (T0) of the dehydration of the GMO headgroups increased. The optimal concentration found for structural stabilization of the HII mesophase was 10 wt% PC, since it imparted the strongest bonding at the interfacial layer and increased the association between the lipid tails. Within the HII cluster, TAG percolated and shifted between the hexagonal rods themselves.The present study demonstrated the benefit of controlling the critical temperature of the HII mesophase partial dehydration and softening, as well as the percolation of TAGs. These factors influence the diffusion mode of embedded drugs in the physiological temperature range.

Interactions of surfactants in nonionic/anionic reverse hexagonal mesophases and solubilization of α-chymotrypsinogen A

In an attempt to form H II mesophases at room temperature we prepared lyotropic liquid crystals with two surfactants of the same lipophilic tails (glycerol monooleate, GMO, and oleyl lactate, OL) but differing in the size and charge of the headgroups. Increasing OL concentration significantly affected the hydration of the headgroups and subsequently the lipids packing. At low OL content the cubic mesophase was formed, while at higher OL contents the formation of hexagonal mesophase was favored. It was assumed that OL competed on the water binding, tuning the headgroups’ curvature and the packing parameter inducing the formation of reverse hexagonal mesophase. It was detected that cubic mesophase transformed upon heating to hexagonal structures. The hexagonal mesophases, which were formed both immediately after preparation and after aging, remained stable at elevated temperatures. α-Chymotrypsinogen was solubilized into the obtained LLCs at relatively high concentration (up to 1 wt%). The lattice parameter of the host LLCs exhibited a decrease as a function of the protein content. This process was assigned to partial dehydration of the GMO polar moieties in favor to CTA hydration. Generally speaking, the present study indicated that adding anionic to nonionic lipid is highly beneficial to gain additional compositional and structural characteristics of LLCs.

Synergistic cosolubilization of omega-3 fatty acid esters and CoQ 10 in dilutable microemulsions

Water-dilutable microemulsions were prepared and loaded with two types of omega-3 fatty acid esters (omega-3 ethyl esters, OEE; and omega-3 triacylglycerides, OTG), each separately and together with ubiquinone (CoQ 10). The microemulsions showed high and synergistic loading capabilities. The linear fatty acid ester (OEE) solubilization capacity was greater than that of the bulky and robust OTG. The location of the guest molecules within the microemulsions at any dilution point were determined by electrical conductivity, viscosity, DSC, SAXS, cryo-TEM, SD-NMR, and DLS. We found that OEE molecules pack well within the surfactant tails to form reverse micelles that gradually, upon water dilution, invert into bicontinuous phase and finally into O/W droplets. The CoQ 10 increases the stabilization and solubilization of the omega-3 fatty acid esters because it functions as a kosmotropic agent in the micellar system. The hydrophobic and bulky OTG molecule strongly interferes with the tail packing and spaces them significantly – mainly in the low and medium range water dilutions. When added to the micellar system, CoQ 10 forms some reverse hexagonal mesophases. The inversion into direct micelles is more difficult in comparison to the OEE system and requires additional water dilution. The OTG with or without CoQ 10 destabilizes the structures and decreases the solubilization capacity since it acts as a chaotropic agent to the micellar system and as a kosmotropic agent to hexagonal packing. These results explain the differences in the behavior of these molecules with vehicles that solubilize them in aqueous phases. Temperature disorders the bicontinuous structures and reduces the supersaturation of the system containing OEE with CoQ 10; as a result CoQ 10 crystallization is retarded.

Structural Effects of Insulin-Loading into HII Mesophases Monitored by Electron Paramagnetic Resonance (EPR), Small Angle X-ray Spectroscopy (SAXS), and Attenuated Total Reflection Fourier Transform Spectroscopy (ATR-FTIR)

Insulin entrapment within a monoolein-based reverse hexagonal (H(II)) mesophase was investigated under temperature-dependent conditions at acidic (pH 3) and basic (pH 8) conditions. Studying the structure of the host H(II) system and the interactions of insulin under temperature-dependent conditions has great impact on the enhancement of its thermal stabilization and controlled release for the purposes of transdermal delivery. Small angle X-ray spectroscopy (SAXS) measurements show that pH variation and/or insulin entrapment preserve the hexagonal structure and do not influence the lattice parameter. Attenuated total reflection Fourier transform spectroscopy (ATR-FTIR) spectra indicate that, although insulin interacts with hydroxyl groups of GMO in the interface region, it is not affected by pH variations. Hence different microenvironments within the H(II) mesophase were monitored by a computer-aided electron paramagnetic resonance (EPR) analysis using 5-doxylstearic acid (5-DSA) as a pH-dependent probe. The microviscosity, micropolarity, order of systems, and distribution of the probes in different microenvironments were influenced by three factors: temperature, pH, and insulin solubilization. When the temperature is increased, microviscosity and order parameters decreased at both pH 3 and 8, presenting different decrease trends. It was found that, at pH 3, the protein perturbs the lipid structure while "pushing aside" the un-ionized 5-DSA probe to fit into the narrow water cylinders. At the interface region (pH 8), the probe was distributed in two differently structured environments that significantly modifies by increasing temperature. Insulin loading within the H(II) mesophase decreased the order and microviscosity of both the microenvironments and increased their micropolarity. Finally, the EPR analysis also provides information about the unfolding/denaturation of insulin within the channel at high temperatures.

The role of glycerol and phosphatidylcholine in solubilizing and enhancing insulin stability in reverse hexagonal mesophases

The potential of reverse hexagonal mesophases based on monoolein (GMO) and glycerol (as cosolvent) to facilitate the solubilization of proteins, such as insulin was explored. HII mesophases composed of GMO/decane/water were compared to GMO/decane/glycerol/water and GMO/phosphatidylcholine (PC)/decane/glycerol/water systems. The stability of insulin was tested, applying external physical modifications such as low pH and heat treatment (up to 70°C), in which insulin is known to form ordered amyloid-like aggregates (that are associated with several neurodegenerative diseases) with a characteristic cross β-pleated sheet structure.The impact of insulin confinement within these carriers on its stability, unfolding, and aggregation pathways was studied by combining SAXS, FTIR, and AFM techniques. These techniques provided a better insight into the molecular level of the “component interplay” in solubilizing and stabilizing insulin and its conformational modifications that dictate its final aggregate morphology.PC enlarged the water channels while glycerol shrank them, yet both facilitated insulin solubilization within the channels.The presence of glycerol within the mesophase water channels led to the formation of stronger hydrogen bonds with the hosting medium that enhanced the thermal stability of the protein and remarkably affected the unfolding process even after heat treatment (at 70°C for 60min).

Controlled embedment and release of DNA from lipidic reverse columnar hexagonal mesophases

DNA–lipid interactions have important implications for biological functions, gene therapy and biotechnology. In the present work, we exploit hydrogen bonding and ionic interactions between lipids and DNA to control the entrapment, the binding and the release properties of DNA confined within the water channels of reverse hexagonal columnar phases. Two lipid formulations were considered, consisting of glycerol monooleate/tricaprylin and glycerol monooleate/oleyl amine/tricaprylin, yielding the nonionic and cationic-based systems, respectively. In the presence of water, or water–DNA dilute solutions, both formulations led to the formation of reverse hexagonal columnar mesophases. To study the confinement of DNA in the reverse hexagonal mesophases, and to understand its interactions with the nonionic and cationic lipid formulations, we relied on small-angle X-ray scattering (SAXS) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. The release of the DNA from these hosting systems in excess water was monitored by UV spectrophotometry and single molecule atomic force microscopy (AFM). In the case of the nonionic columnar system, DNA confined within the water cylinders, was stabilized by hydrogen bonding with the lipid polar heads, as revealed by the dehydration of the glycerol monooleate polar headgroups and a decrease in the water channel diameter. The diffusion of DNA out of the mesophase water channels was found to occur in three steps correlated with the different contour lengths of the DNA fragments generated enzymatically from the same pristine DNA macromolecule. In contrast, the presence of a low dose of cationic surfactants in the formulation enabled strong electrostatic interactions with the DNA molecules, swelling the water cylinders and entirely suppressing the release of DNA. These results show that lipidic mesophases constitute an appealing, fully biocompatible carrier, allowing a fine control on the encapsulation and delivery of DNA in excess water environment.

Crystallization of cyclosporin A in lyotropic reverse hexagonal liquid crystals

In this communication we demonstrate for the first time that lyotropic reverse hexagonal mesophase can serve as a crystallization medium for a hydrophobic peptide, resulting in high quality single crystals suitable for crystallographic analysis. The obtained crystals of cyclosporin A enabled excellent X-ray data collection, diffracting to a resolution limit of 1.0 Å. Current findings open a new perspective in the field of crystallization of biological macromolecules in lyotropic mesophases.

Temperature-dependent behavior of lysozyme within the reverse hexagonal mesophases (H II)

This manuscript is the second part of a study on the structural behavior of lysozyme-loaded reverse hexagonal mesophases. In the current paper we focused mainly on the mutual temperature-dependency relationship between the protein and the mesophase. The conformational stability of the enzyme and the structural effects on the host system were characterized using small-angle X-ray scattering (SAXS), ATR-FTIR spectroscopy, fluorescence, and rheological measurements. It was found that the mesophase does not change the solubilized lysozyme (LSZ) active site conformation. The obtained data suggested that LSZ embedment within the H II mesophase improved its thermal stability by hampering its helical structure destruction, apparently due to hydrogen bonding of the protein with monoolein polar heads. Examination of the structural parameters of the hexagonal carrier revealed a strong thermal dependency. The lattice parameter of both empty and LSZ-loaded systems had a similar temperature-dependent behavior. However, comparing the domain size of the LSZ-loaded system to the empty system showed different trends. LSZ incorporation induced a decrease in crystal size and lower order at room temperature. Nevertheless, an increase in domain size was triggered by the enzyme at elevated temperatures, in contrast to its decrease in the empty carriers. Rheological measurements showed concentration-dependent elasticity in the presence of LSZ compared to the empty system, which took place in a concentration-dependent manner at all examined temperatures. Up to 60 °C, the elasticity of the LSZ-loaded hexagonal systems decreased with temperature increase. This finding was interpreted in the context of weakening and/or cleaving of the monoolein hydroxyls’ interactions with the protein, leading to partial reconstitution of the initially low domain size and elasticity decrease. However, in the range of 60–75 °C (in most systems), the prevailing effect was thermally induced dehydration of the monoglyceride hydrophilic heads, which imposed elasticity increase, owing to enhanced flow ability of the liquid crystalline structure.