Lyotropic Liquid Crystalline Systems Research Articles

Tandem "One-Shot" Measurement of Residual Chemical Shift Anisotropy and Residual Dipolar Coupling using Biphasic Supramolecular Peptide Liquid Crystals.

Both solitary and tandem applications of residual chemical shift anisotropy (RCSA) and residual dipolar coupling (RDC) show great potential for the structural and configurational determination of organic molecules. A critical component of both RDC and RCSA methodologies is the alignment medium, whose availability is limited, especially for RCSA measurement. Moreover, reported RDC and RCSA acquisitions mainly rely on two experiments conducted under two different conditions, which are relatively time-consuming and easily cause experimental errors. Herein, a biphasic supramolecular lyotropic liquid crystalline (LLC) system was developed through the self-assembly of C21H43-CONH-V4K3-CONH2, which could act as an alignment medium for not only RDC but also RCSA extraction in DMSO-d6. Notably, the RCSA extraction was easily achieved via one-shot measurement from a single one-dimensional 13C NMR experiment, with no need for special instruments, devices, and correction. Relying on the biphasic LLC medium, meanwhile, RDC data were simply extracted from a single F1-coupled HSQC experiment, different from the standard protocol that requires two spectral acquisitions corresponding to the isotropic and anisotropic conditions. Collectively, the biphasic LLC medium is applicable for tandem RCSA and RDC measurements in one single sample, advancing the stereochemical elucidation of molecules of interest.

Tandem "One-Shot" Measurement of Residual Chemical Shift Anisotropy and Residual Dipolar Coupling using Biphasic Supramolecular Peptide Liquid Crystals.

Both solitary and tandem applications of residual chemical shift anisotropy (RCSA) and residual dipolar coupling (RDC) show great potential for the structural and configurational determination of organic molecules. A critical component of both RDC and RCSA methodologies is the alignment medium, whose availability is limited, especially for RCSA measurement. Moreover, reported RDC and RCSA acquisitions mainly rely on two experiments conducted under two different conditions, which are relatively time-consuming and easily cause experimental errors. Herein, a biphasic supramolecular lyotropic liquid crystalline (LLC) system was developed through the self-assembly of C21H43-CONH-V4K3-CONH2, which could act as an alignment medium for not only RDC but also RCSA extraction in DMSO-d6. Notably, the RCSA extraction was easily achieved via one-shot measurement from a single one-dimensional 13C NMR experiment, with no need for special instruments, devices, and correction. Relying on the biphasic LLC medium, meanwhile, RDC data were simply extracted from a single F1-coupled HSQC experiment, different from the standard protocol that requires two spectral acquisitions corresponding to the isotropic and anisotropic conditions. Collectively, the biphasic LLC medium is applicable for tandem RCSA and RDC measurements in one single sample, advancing the stereochemical elucidation of molecules of interest.

Wetting and Adhesive Properties of Biopolymer-Based Organized Condensed Phases as Drug Delivery Systems

Lyotropic liquid crystalline systems are of great interest as carriers of biological substances for targeted delivery, mainly for transdermal administration of drugs and their application to the skin and mucous membranes. The wetting and adhesive interactions of lyomesophases and gel based on a chitosan polysaccharide in lactic acid solution on a glass substrate (base surface) and the surface of a semi-permeable polytetrafluoroethylene membrane (model of epidermis horny layer) were studied. The effect of the riboflavin drug (vitamin B2) on the surface tension of studied samples and the amount of adhesion work has been established. It is shown that biocompatible chitosan-containing systems can be used as drug carriers for various biomedical purposes, including transdermal drug delivery.

A novel droplet-based approach to study phase transformations in lyotropic liquid crystalline systems

HypothesisLyotropic liquid crystals (LLC) and their phase transformations in response to stimuli have gathered much interest for controlled and ‘on-demand’ drug applications. Bulk methods of preparation impose limitations on studying the transformations, especially induced by compositional changes, such as enzymatic changes to lipid structure. Here we hypothesise that controlled microfluidic production and coalescence of dissimilar aqueous and lipid droplets emulsified in a third mutually immiscible liquid will provide a new approach to the spatio-temporal study of structure formation in lyotropic liquid crystalline materials. ExperimentsSeparate lipid and aqueous droplets, dispersed in a fluorocarbon oil were generated using a microfluidic format. The chip, prepared as a hybrid polydimethylsiloxane (PDMS) and glass microfluidic device, was constructed to enable in-situ acquisition of time-resolved synchrotron small angle X-ray scattering (SAXS) and crossed polarised light microscopy of the coalesced droplets to determine the structures present during aging. FindingsJanus-like droplets formed upon coalesce, with distinct lipid and aqueous portions with a gradient between the two sides of the merged droplet. SAXS and polarised light microscopy revealed a progression of mesophases as the lipid portion was hydrated by the aqueous portion via the diffusion limited interface which separated the portions. Thus demonstrating, on a droplet scale, a new approach for studying the phase transformation kinetics and identification of non-equilibrium phase in droplet-based lyotropic liquid systems.

Evaluation of the utility of isotropic pitches as solvent components of spinnable mesophase pitch precursors for highly graphitizable functional carbon materials

Spinnable mesophase pitch (SMP) is an important graphitizable precursor for high-performance carbon materials. Generally, SMPs show fully developed anisotropic texture, and the pitches contain isotropic contents more than 30 wt%, which plays the role of solvent for the mesogenic components in the lyotropic liquid crystalline system of the pitch. Here, we prepared SMP by blending the mesogenic components of AR mesophase pitch with various isotropic pitches to evaluate the usability of isotropic pitches as solvents. The mesogenic components were prepared by tetrahydrofuran fractionation of AR mesophase pitch. Isotropic pitches with a softening point of 140–220 °C were prepared separately by simple heat treatment of slurry oil (SO) and coal tar pitch (CTP). SMPs were prepared by thermal blending of the above mentioned mesogenic components and isotropic pitches in various blending ratios. CTP-derived isotropic pitch showed better solvent performance than a SO-derived pitch in terms of anisotropic texture. SMP prepared by blending of the mesogenic components and CTP-derived isotropic pitch with a softening point of 180 °C at the ratio of 4/6 (w/w) showed almost 100% anisotropic texture; the carbon fiber derived from the pitch showed tensile strength of 2.7 GPa and Young’s modulus of 470 GPa after graphitization at 2,800 °C.

Correlation between molecular stacking and anisotropic texture in spinnable mesophase pitch

The correlation of the anisotropic texture and (002) the molecular stacking property of spinnable mesophase pitch (SMP) was closely examined. SMP was found to be a specific solution consisting of mesogenic and solvent components, and the mesogenic component was composed of a cluster unit of (002) stacked molecular sheets. The anisotropic texture of SMP was strongly correlated with the height of (002) molecular stacking. When the concentration ratio of the mesogenic component to the solvent component was higher than the threshold concentration, the SMP always had 100 vol% anisotropic texture and a similar or larger number of stacked (002) sheets compared with its mesogenic component in both the solid and molten states. The solvent component, in both lamellar and hexagonal phases, assisted orientation of mesogenic molecules and rearrangement of mesogenic cluster units, thereby inducing a higher degree of graphitization than that of the solvent-free mesophase pitch. A schematic phase model of SMP was proposed based on a lyotropic liquid crystalline system and a hierarchical domain model.

Membrane Protein Structures in Lipid Bilayers; Small-Angle Neutron Scattering With Contrast-Matched Bicontinuous Cubic Phases.

This perspective describes advances in determining membrane protein structures in lipid bilayers using small-angle neutron scattering (SANS). Differentially labeled detergents with a homogeneous scattering length density facilitate contrast matching of detergent micelles; this has previously been used successfully to obtain the structures of membrane proteins. However, detergent micelles do not mimic the lipid bilayer environment of the cell membrane in vivo. Deuterated vesicles can be used to obtain the radius of gyration of membrane proteins, but protein-protein interference effects within the vesicles severely limits this method such that the protein structure cannot be modeled. We show herein that different membrane protein conformations can be distinguished within the lipid bilayer of the bicontinuous cubic phase using contrast-matching. Time-resolved studies performed using SANS illustrate the complex phase behavior in lyotropic liquid crystalline systems and emphasize the importance of this development. We believe that studying membrane protein structures and phase behavior in contrast-matched lipid bilayers will advance both biological and pharmaceutical applications of membrane-associated proteins, biosensors and food science.

Development of a Liquid Crystal Formulation that Can Penetrate the Stratum Corneum for Intradermal Delivery of Small Interfering RNA.

Topical delivery of small interfering RNA (siRNA) can be an attractive method for the treatment of skin diseases and improving the quality of life of patients. However, it is difficult for siRNA to pass through the two major barriers of the skin: the stratum corneum (SC) and tight junctions. We have previously reported that atopic dermatitis of skin without the SC can be efficiently treated by the intradermal administration of trans-activator of transcription (Tat) peptide and AT1002 (tight junction opening peptide). However, novel drug delivery systems are needed for effective SC penetration. Therefore, in the present study, we aimed to develop a lyotropic liquid crystalline (LC) system containing Tat and AT1002 for effective siRNA penetration through the SC. An LC formulation was prepared using selachyl alcohol and purified water, and its skin penetration ability was evaluated. No fluorescence was observed in mouse skin treated with a siRNA solution, as there was no intradermal localization of siRNA from naked siRNA. However, intradermal delivery of siRNA was remarkable and extensive with the LC formulation containing both Tat and AT1002. Semiquantitative analysis by brightness measurement revealed that the LC formulation containing both Tat and AT1002 had significantly enhanced intact skin permeability than other formulations. These results show that the functional peptides in the LC formulation increased SC penetration and intradermal delivery in the healthy skin. Therefore, this novel LC system may be useful in the treatment of various skin diseases.

Correlation between Molecular Stacking and Anisotropic Texture in Spinnable Mesophase Pitch

The correlation of the anisotropic texture and (002) molecular stacking property of spinnable mesophase pitch was closely examined. Spinnable mesophase pitch was found to be a specific solution which consisted of mesogenic and solvent components. Here, the mesogenic component composed of the cluster unit of the (002) stacked molecular sheets. In addition, the anisotropic texture of spinnable mesophase pitch showed a strong correlation with the height of (002) molecular stacking. When the concentration of mesogenic component to the solvent one is higher than the threshold concentration, spinnable mesophase pitch always showed 100 vol% anisotropic texture and the similar or larger number of stacked (002) sheets than that of its mesogenic component in both the solid and melt states. The solvent component in the lamellar and hexagonal phases may help the orientation of mesogenic molecules and rearrangement of mesogenic cluster units, inducing a higher graphitization degree than that of the mesophase pitch with solvent-free. The schematic phase model of spinnable mesophase pitch was proposed by the authors based on a lyotropic liquid crystalline system and the hierarchical domain model.

Lipids from algal biomass provide new (nonlamellar) nanovectors with high carrier potentiality for natural antioxidants

Lipid mesophases are lyotropic liquid crystalline systems which differ from liposomes and other globular aggregates in dilute regimes due to their inner ordering. It is known that natural lipids enable to obtain a rich variety of nanosystems and many of them have been proposed as delivery agents for bioactive compounds. Due to their packing parameters, several classes of lipids found in natural sources are able to self-assemble into nonlamellar structures. Among lipids occurring in plants and algae, triglycerides display this tendency. In the present study we examine new nanosystems built with lipids extracted from the marine microalga Nannochloropsis sp and their use as carriers for lipophilic antioxidants. The antioxidants studied, curcumin and tocopherol were encapsulated with high rate in the carriers. The physico-chemical characterization of plain and loaded vectors showed their structure and localization site, as well as the structure-functionality relationship related to potential drug delivery. The results show that the cargo molecules play an active role in driving the interactions which characterize the overall structure of the aggregates. The systems studied showed several coexisting mesophases, the most predominant structure being of cubic symmetry.

The Evaluations of Menthol and Propylene Glycol on the Transdermal Delivery System of Dual Drug-Loaded Lyotropic Liquid Crystalline Gels.

This study aimed to evaluate the effects of two different structural alcohol permeation enhancers (menthol and propylene glycol) on the internal structure and in vitro properties of the dual drug-loaded lyotropic liquid crystalline (LLC) gels. The LLC gels were prepared and characterized by polarized light microscopy, small-angle X-ray scattering, differential scanning calorimetry, attenuated total reflectance-Fourier transform infrared spectrum, and rheology. Based on the results, the inner structure of the gels was QII mesophase and exhibited a pseudoplastic fluid behavior. The level of internal order in the LLC mesophase would be affected by introduced 2wt% menthol (MEN) and propylene glycol (PG). The in vitro release experiment showed that the release behavior of sinomenine hydrochloride (SH) and cinnamaldehyde (CA) from the LLC system was dominated by Fickian diffusion (n < 0.43). MEN and PG had the opposite effects on the release of hydrophilic SH, while the MEN and PG both increased the release of lipophilic drug CA. Furthermore, in vitro permeation studies indicated that MEN and PG could both improve the skin permeability of SH and CA, and MEN displayed more pronounced enhancement. All the samples showed no skin irritation on the normal rat skin. Collectively, in our research, monoterpenoid MEN exhibited a better penetration-promoting effect than straight-chain fatty alcohol PG on the dual drug-loaded LLC system.

Hexaarylbiimidazoles(HABI)-functionalized lyotropic liquid crystalline systems as visible light-responsive materials

Hexaarylbiimidazoles (HABIs) are a promising class of photoswitchable molecule that have received little attention in the literature. Among them, (2,2′-dimethoxydiphenylimidazole)-1,1′-binaphthyl (HABI1) displays unusual negative photochromism and is responsive to green light. This study investigates the potential of HABIs to serve as photo-responsive actuators controlling the structure of lyotropic liquid crystalline (LLC) materials. HABI1 with four methyl chains and HABI2 with four dodecyl chains were synthesized. Time resolved small angle X-ray scattering was used to characterize the potential disruptive effects of HABIs on the nanostructure of LLC systems. HABIs underwent rapid isomerization under irradiation, with a very slow reversion in the dark in toluene and in the LLC matrix, demonstrating excellent stability and photo-fatigue resistant. HABIs completely triggered phase transitions in the phytantriol-based materials, and HABI2 generated a greater disruption than HABI1 on the lipid packing due to the enhanced steric influence. Tuning the lipid composition yielded systems that transitioned from a “slow release” lamellar phase to a “burst release” bicontinuous cubic phase upon light irradiation. Such systems therefore may exhibit a triggered release behavior upon a short time of irradiation, showing great potential in “on demand” drug delivery.

Ultrathin films of functionalised single-walled carbon nanotubes: a potential bio-sensing platform

ABSTRACT The Langmuir monolayer is a special class of lyotropic liquid crystalline system wherein phase transition essentially depends on surface density, temperature and ion-content in the aqueous medium. The variety of surface phases can be transferred onto devices by the Langmuir–Blodgett (LB) technique. The Langmuir monolayer of pristine single-walled carbon nanotubes (SWCNTs) exhibited gas and liquid-like phases. The LB film of SWCNTs shows target surface pressure dependent interesting morphologies. The methane gas sensing using parallel alignment of SWCNTs was found to be better than that of randomly oriented SWCNTs. The SWCNTs can be functionalised chemically to enhance the ease of film processability and affinity towards analytes. These are essential parameters for the development of a sensor. In this article, we present our work on Langmuir monolayer and LB films of octadecylamine functionalised SWCNTs (ODACNTs) and its sensing application towards bio-analytes, e.g. L-aspartic acid and bovine serum albumin. The sensing performance of LB film of ODACNTs was compared with that of spin-coated films of ODACNTs. The sensing performance of LB films of ODACNTs indicated a potential platform for bio-sensing application.

Synthesis of copper (II) oxide nanocorals from a triton X-100-based lyotropic liquid crystalline system

Cu(II) oxide nanocorals were synthesized for the first time from a lyotropic liquid crystalline system formed from triton X-100 and water. The nanocorals were prepared based on a simple precipitation route, and then characterized by field emission scanning electron microscopy and X-ray diffraction patterns. The nanocorals provided a porous ensemble which comprised adhered nanorods of <50 nm in diameter. XRD pattern confirmed the crystalline structure of CuO with a grain size of ≈30 nm. Electrochemical behavior of the nanocorals was preliminary evaluated in an alkaline solution, and they represented a potential for hydrogen peroxide determination.

Impact of Topology on the Characteristics of Water inside Cubic Lyotropic Liquid Crystalline Systems.

Water molecules present inside the lipid-based cubic liquid crystalline phases are found to play a major role in wide range of applications, such as protein crystallization, virus detection, delivery of drug and biomolecules, etc. In this regard, it is crucial to elucidate static and dynamic properties of the water molecules in the nanochannels and to explore the effect of geometrical topology on the nature of the water inside the different cubic phases. In the present work, we have incorporated two probes, coumarin-343 (C-343) and coumarin-480 (C-480), in two cubic phases with different symmetries, namely gyroid ( Ia3 d) and double diamond ( Pn3 m) with the same water content (22%), to probe the micropolarity, the microviscosity, and the hydration dynamics at different hydrophobic depths in the mesophases. Steady state results estimate the polarity at the lipid-water interface to be similar to that of ethanol, and the polarity near the more hydrophilic parts of the nanochannel resembles that of ethylene glycol. We have also observed a gradient in the microviscosity inside the LLC nanochannels from time-resolved fluorescence anisotropy studies. The hydration dynamics, which play a key role in the numerous applications of the mesophases, have been probed by the time-dependent Stokes shift method of the two probes, revealing the existence of three kinds of dynamics. The difference in the hydration dynamics inside the two mesophases, where the water molecules confined in the Ia3 d phase exhibit a slower dynamics compared to that in Pn3 m, is the prime importance of this work. The underlying reason for this disparity is majorly associated with the differences in the topology of the two structures including the hydrophobic packing stress, the negative interfacial curvature, and the curvature elastic energy of the lipid-water interface. We believe that this kind of correlation between the structural topology of the different cubic LLC mesophases and nature of the water nanochannel will help to boost the applications of the cubic phases in the future.

Visible light-triggered cargo release from donor acceptor Stenhouse adduct (DASA)-doped lyotropic liquid crystalline nanoparticles

Light-responsive nanocarriers are applicable as non-invasive, highly tunable and precisely controlled drug delivery systems. Here, we report a new nanocarrier system, achieved by doping D1, a type of green light–responsive donor acceptor Stenhouse adduct (DASA), into a lipid-based lyotropic liquid crystalline system. Time-resolved small angle X-ray scattering was used to confirm that the matrix underwent a rapid and fully reversible phase transition from lamellar to inverse cubic phase upon irradiation with green light (532 nm), reverting back on removal of light. Fluorescein isothiocyanate–dextran (FD4) was used as a model hydrophilic cargo. The release of cargo upon varying irradiation parameters was investigated in vitro which showed that irradiation can trigger a burst release of FD4 upon phase transition. This additive shows promise for the development of new visible light-activated, “on demand” drug delivery systems.

Effect of viscosity, pH and physicochemical parameters of solvent on the aggregation and dielectric behaviour of lyotropic liquid crystals binary mixtures

This paper reports on the synthesis of lyotropic liquid crystalline phases using cetyl pyridinium chloride and sodium dodecyl sulphate in the aqueous (water) and non-aqueous solvent (glycerol) of varying polarity and viscosities. Various crystal-like, liquid-like and liquid crystalline phases are seen in the different solvent media at the expense of increasing concentration of surfactants. It is interesting to highlight that highly viscous and little acidic (pH≈6) mixtures produce more ordered structures comparing to other. Aggregation of cetyl pyridinium chloride in both solvents is found thermally driven process as calorimetric transition confirmed the growth of the lyotropic phases at a higher temperature (331–345K) than 303K. Quenching has been evolved as the proficient technique to bring the higher temperature lyotropic liquid crystalline ordering to the room temperature without breaking the symmetry. Structural and polarizing optical microscopy measurement reveals that viscosity plays vital role on the aggregation in lyotropic liquid crystalline systems as glycerol based quenched and as-synthesized lyotropic liquid crystalline phases are found more ordered than other. Dielectric dynamics reveals that quenched cetyl pyridinium chloride/glycerol-based lyotropic liquid crystalline phases show higher dielectric constant; however, the reverse is true for the sodium dodecyl sulphate/glycerol lyotropic liquid crystalline phases. Dc conductivity of the order 10−5S/m is one of the significant finding of this study, which open up the application perspective of these phases.

Development and In Vitro Evaluation of Lyotropic Liquid Crystals for the Controlled Release of Dexamethasone.

In this study, amphiphilic polymers were investigated as biomaterials that can control dexamethasone (DXM) release. Such materials present interfacial properties in the presence of water and an oily phase that can result in lyotropic liquid crystalline systems (LLCS). In addition, they can form colloidal nanostructures similar to those in living organisms, such as bilayers and hexagonal and cubic phases, which can be exploited to solubilize lipophilic drugs to sustain their release and enhance bioavailability. It was possible to obtain lamellar and hexagonal phases when combining polyoxyethylene (20) cetyl ether (CETETH-20) polymer with oleic acid (OA), N-methylpyrrolidone (P), isopropyl myristate (IM), and water. The phases were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological, textural, and bioadhesion analyses followed by an in vitro release assay. All samples showed elastic behavior in the rheology studies and hexagonal samples containing P and IM showed the highest adhesiveness. The drug release profile of all LLCS presented an average lag time of 3 h and was best fitted to the Korsmeyer-Peppas and Weibull models, with controlled release governed by a combination of diffusion and erosion mechanisms. These systems are potential carriers for DXM and can be explored in several routes of administration, providing potential advantages over conventional pharmaceutical forms.

An injectable in situ gel with cubic and hexagonal nanostructures for local treatment of chronic periodontitis

Periodontitis is a chronic bacterial infection, and its effective treatment is dependent on the retention of antibiotics of effective concentrations at the periodontal pockets. In this study, a solution–gel based inverse lyotropic liquid crystalline (LLC) system was explored to deliver metronidazole to the periodontal pockets for local treatment of periodontitis. It was found that the metronidazole-loaded LLC precursor spontaneously transformed into gel in the presence of water in the oral cavity. The low viscosity of the precursor would allow its penetration to the rather difficult to reach infection sites, while the adhesiveness and crystalline nanostructures (inverse bicontinuous cubic Pn3m phase and inverse hexagonal phase) of the formed gel would permit its firm adhesion to the periodontal pockets. The LLC system provided sustained drug release over one week in vitro. Results from in vivo study using a rabbit periodontitis model showed that the LLC system was able to maintain the metronidazole concentrations in the periodontal pockets above the minimum inhibition concentration for over 10 days without detectable drug concentration in the blood. Owing to the spontaneous solution–gel transition in the periodontal pockets and unique liquid crystalline nanostructures, the LLC in situ gel provided effective treatment of periodontitis for a prolonged period of time with reduced systematic side effects, compared to metronidazole suspension which was effective for 24 h with detectable metronidazole concentrations in the blood after 6 h.

Dynamics of different steps of the photopyrolytic cycle of an eminent anticancer drug topotecan inside biocompatible lyotropic liquid crystalline systems

Dynamics of different steps of photopyrolytic processes of an eminent anticancer drug topotecan have been investigated inside different lyotropic liquid crystalline systems.