Lyotropic Liquid Crystalline Research Articles

Limitation and Potential of Lignin-Assisted Stabilisation of Oriented Liquid Crystalline Cellulosic Mesophase

This study aimed at progressing in the fundamental understanding of the lignin-assisted microstructural stabilisation observed in solution-processed materials based on the polymer blend of hydroxypropyl cellulose and hardwood organosolv lignin. Mechanical analysis, polarised infrared spectroscopy and wide-angle X-ray scattering of shear cast blend films revealed that the effect of lignin on the flow-oriented cellulosic mesophase is also valid for blends composed of ethyl cellulose as liquid crystalline matrix polymer and lignin derived oligomers from base-catalysed depolymerisation as dispersed “microstructural cementing agent”. The results underline the significant role of the solvent diffusion between the continuous cellulosic and the dispersed lignin phase, which is ascribed to polymer-/oligomer-solvent interactions. An abundance of the solvent within the lignin phase caused the disruption of the microstructural stabilisation effect. The concept of a balanced proton-donor activity was introduced linking the solvent diffusion with the lyotropic liquid crystalline phase formation, the macro- and microstructural blend morphology and aspects regarding the solution processing.

Lyotropic Liquid Crystalline Based Nasal Spray for Improved Parkinson's Treatment: Enhanced Superior Nasal Tract Deposition and Antioxidation Strategy

AbstractThe blood–brain barrier is one of the serious challenges in the treatment of Parkinson's disease (PD), which severely hinders the drug's brain bioavailability. In this study, a lyotropic liquid crystalline (LLC) based in situ gel nasal spray loaded with the first‐line drug Levodopa (LDA) for PD is developed to resolve this issue based on a nose‐to‐brain drug delivery approach. Specifically, the two key stages of LLC‐based in situ gel nasal spray, droplet deposition, and drug retention are tailored. By adjusting LLC's precursor solution's viscosity, the droplet deposition on the superior nasal tract can be increased by 18 times. Through nasal mucus‐triggered sol–gel transition, the LDA nasal cavity retention is prolonged by three times. The epigallocatechin gallate is incorporated into the LLC‐based in situ gel nasal spray to inhibit the autoxidation of LDA and alleviate the oxidative stress response in PD. The results show that the LLC‐based in situ gel nasal spray has a 26‐fold higher brain bioavailability of LDA compared to oral administration. The PD rats show a significant improvement in behavioral and cognitive disorders after administration. The LLC‐based in situ gel nasal spray is proved to work by reducing oxidative damage. This study is anticipated to offer a promising strategy for the clinical application of LDA.

Preparation and Characterization of Lyotropic Liquid Crystalline Nanoparticles Loaded with Astaxanthin-Rich Oil from Shrimp Waste

Preparation and Characterization of Lyotropic Liquid Crystalline Nanoparticles Loaded with Astaxanthin-Rich Oil from Shrimp Waste

Exciting Novel Polyaspartates: Design, Synthesis, and Photo-Responsive Behavior in Solution and Lyotropic Liquid Crystalline Phase Upon Irradiation with Visible Light.

Many polypeptides form stable, helical secondary structures enabling the formation of lyotropic liquid crystalline (LLC) phases. Contrary to the well-studied polyglutamate, their counterparts based on polyaspartates exhibit a much lower helix inversion barrier. Therefore, the helix sense is not solely dictated by the chirality of the amino acid used, but additionally by the nature and conformation of the polymer sidechain. In this work, polymers responsive to irradiation with visible light are designed achieving conformational transitions from helix-to-coil and helix-to-helix. The synthesis and the application as LLC mesogens of several (co-)polyaspartates bearing ortho-fluorinated azobenzene (FAB) as a photochromic group are presented. Many of the obtained polymers undergo changes in their secondary structure upon E-Z-isomerization of the FAB-containing sidechain. Of special interest are copolymers that exhibit photo-responsive helix inversion without loss of their helical secondary structure. These copolymers form stable LLC phases in helicogenic solvents, where the effect of photo-switching on the macroscopic behavior is studied by NMR spectroscopy. Especially, the irradiation of the different LLC phases of the helix inversion polymers displays a change in the LLC order experienced by the solvent. These peculiar properties are promising for future applications as photo-responsive alignment media for structure elucidation in NMR.

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.

Lyotropic Liquid Crystalline Phase Nanostructure and Cholesterol Enhance Lipid Nanoparticle Mediated mRNA Transfection in Macrophages

AbstractMacrophages are unique immune cells attracting growing attention as a potential candidate for cell‐based therapy for infectious diseases and cancer. Strategies that can reprogramme or gene‐edit macrophages hold potential across a spectrum of acute and chronic conditions. Herein, lipid nanoparticles (LNPs) are developed containing the ionizable lipid SM‐102, helper lipid monoolein which is known for self‐assembly in aqueous solutions into the inverse cubic lyotropic liquid crystalline mesophase, and cholesterol as an mRNA nanocarrier. The immortalized alveolar macrophage cell line (MH‐S cells) is utilized to investigate how cholesterol concentration impacts on mRNA delivery which is further validated using primary mouse alveolar macrophages isolated from the bronchoalveolar compartment and human monocyte derived macrophages. By using high‐throughput synchrotron small angle X‐ray scattering (SAXS), an acidification‐induced non‐ordered to ordered internal nanostructure transition of the formulated LNPs is observed, following the transition sequence of inverse micellar to hexagonal to cubic mesophase in the pH range from 7 to 4. Cholesterol is identified as another crucial component for superior mRNA transfection in macrophages, contributing to nanostructure transition and protein corona variation. Successful ex vivo mRNA transfection is also achieved in primary macrophages, highlighting the prospectivity of reprogramming macrophages as a cell therapy for lung diseases.

Nanotubes of a Different Kind: Stoichiometry and Geometry of the Orange II/γ-Cyclodextrin Complex in Water.

Orange II (O-II), a water-soluble ionic azo dye, aggregates and eventually forms needle-like crystals at concentrations greater than 0.15 M. However, when equimolar amounts of γ-cyclodextrin (γ-CD) are added to solutions containing O-II at 0.025 M or higher, the solution's appearance rapidly changes presenting a viscous, birefringent liquid, a lyotropic liquid crystalline solution. Birefringence is absent when viewing aqueous solutions of only O-II or γ-CD at concentrations greater than 0.03 M. Using ultraviolet-visible (UV-vis) and fluorescence spectroscopy, coupled with conductivity measurements, we postulate a structure for the basic "building block" of the self-assembly that eventually gives rise to a rodlike superstructure, leading to the formation of a lyotropic liquid crystalline phase.

A Long-Acting Lyotropic Liquid Crystalline Implant Promotes the Drainage of Macromolecules by Brain-Related Lymphatic System in Treating Aged Alzheimer's Disease.

Numerous evidence has demonstrated that the brain is not an immune-privileged organ but possesses a whole set of lymphatic transport system, which facilitates the drainage of harmful waste from brains to maintain cerebral homeostasis. However, as individuals age, the shrinkage and dysfunction of meningeal and deep cervical lymphatic networks lead to reduced waste outflow and elevated neurotoxic molecules deposition, further inducing aging-associated cognitive decline, which act as one of the pathological mechanisms of Alzheimer's disease. Consequently, recovering the function of meningeal and deep cervical lymph node (dCLNs) networks (as an important part of the brain waste removal system (BWRS)) of aged brains might be a feasible strategy. Herein we showed that the drug brain-entering efficiency was highly related to administration routes (oral, subcutaneous, or dCLN delivery). Besides, by injecting a long-acting lyotropic liquid crystalline implant encapsulating cilostazol (an FDA-approved selective PDE-3 inhibitor) and donepezil hydrochloride (a commonly used symptomatic relief agent to inhibit acetylcholinesterase for Alzheimer's disease) near the deep cervical lymph nodes of aged mice (about 20 months), an increase of lymphatic vessel coverage in the nodes and meninges was observed, along with accelerated drainage of macromolecules from brains. Compared with daily oral delivery of cilostazol and donepezil hydrochloride, a single administered dual drugs-loaded long-acting implants releasing for more than one month not only elevated drug concentrations in brains, improved the clearing efficiency of brain macromolecules, reduced Aβ accumulation, enhanced cognitive functions of the aged mice, but improved patient compliance as well, which provided a clinically accessible therapeutic strategy toward aged Alzheimer's diseases.

Controlling the Nematic Liquid Crystallinity of Cellulose Nanocrystals with an Alcohol Ethoxy Sulfonate Surfactant.

Cellulose nanocrystals (CNCs) are biobased colloidal nanorods that have unlocked new opportunities in the area of sustainable functional nanomaterials including structural films and coatings, biomedical devices, energy, sensing, and composite materials. While selective light reflection and sensing develop from the typical chiral nematic (cholesteric, Nem*) liquid crystallinity exhibited by CNCs, a wealth of technologies would benefit from a nematic liquid crystal (LC) with CNC uniaxial alignment. Therefore, this study answers the central question of whether surfactant complexation suppresses CNC chirality in favor of nematic lyotropic and thermotropic liquid crystallinity. Therein, we use a common surfactant having both nonionic and anionic blocks, namely, oligo(ethylene glycol) alkyl-3-sulfopropyl diether potassium salt (an alcohol ethoxy sulfonate (AES)). AES forms complexes with CNCs in toluene (a representative for nonpolar organic solvent) via hydrogen bonding with an AES' oligo(ethylene glycol) block. A sufficiently high AES weight fraction endows the dispersibility of CNC in toluene. Lyotropic liquid crystallinity with Schlieren textures containing two- and four-point brush defects is observed in polarized optical microscopy (POM), along with the suppression of the cholesteric fingerprint textures. The results suggest a nematic (Nem) phase in toluene. Moreover, thermotropic liquid crystallinity is observed by incorporating an excess of AES, in the absence of an additional solvent and upon mild heating. The Schlieren textures suggest a nematic system that undergoes uniaxial alignment under mild shear. Importantly, replacing AES with a corresponding nonionic surfactant does not lead to liquid crystalline properties, suggesting electrostatic structural control of the charged end group of AES. Overall, we introduce a new avenue to suppress CNC chirality to achieve nematic structures, which resolves the long-sought uniaxial alignment of CNCs in filaments, composite materials, and optical devices.

Large-scale production of graphene encapsulated silicon nanospheres as flexible anodes for lithium ion batteries

Silicon (Si) is regarded as the most promising anode candidate for the next high energy density lithium ion batteries (LIBs) owing to its highest theoretical specific capacity and low lithiation potential. However, the practical application of Si-based materials is severely limited due to their enormous volume expansion, which leads to the breakdown of the electrode structure and shortens the cycle life. Herein, we successfully fabricated a free-standing graphene encapsulated silicon nanospheres (Si/rGO) film through homogenizing nano-Si in the lyotropic liquid crystallinity of graphene oxide (GO), followed by coating on the PET substrate and hot pressing technology. For the first time during the preparation process, the dispersion of nano-Si in deionized water was quantitatively characterized through real-time measurements of zeta potential and average particle size. Benefiting from the highly ordered layer-to-layer stacking and dense framework, the as-prepared Si/rGO film shows a high initial discharge capacity of 1727.2 mAh/g at 200 mA/g and superior cycling stability (1024.2 mAh/g over 200 cycles). This straightforward and easy-to-implement method can be used for industrial-scale production through continuous feeding.

Influence of Ionic Liquid and Light Intensity on a Polymer Nanostructure Formed in Lyotropic Liquid Crystalline Templates.

Utilizing self-assembled lyotropic liquid crystal (LLC) templates with radical photopolymerization shows promise in controlling polymer structure on the nanometer scale This control of nanostructure allows tailoring and enhancement of material properties not attainable in traditional polymerization in applications including hydrogels and stimuli-responsive systems. However, thermodynamically driven phase separation between the polymer and LLC templates often hinders the control of local polymer order and resultant polymer properties. This study investigates an alternative method to control the hydrogel nanostructure and avoid phase separation using imidazolium ionic liquids (ILs) in the LLC template while modulating the light intensity used in photopolymerization. The addition of the IL improves the thermodynamic stability and enhances the polymerization rate in the LLC system. The degree of LLC nanostructure retention is increased by increasing light intensities during polymerization. In addition, intermediate concentrations of cross-linker allow a balance between phase stability and cross-linking to lock in LLC morphology. With enhanced retention, the maximum water uptake is significantly higher compared with isotropic controls. These results demonstrate a method to increase the structure on the nanometer scale of a polymer by combining the addition of ILs with the proper selection of light intensity and cross-link density that allows access to unique hydrogel properties. These templated polymers demonstrate enhanced swelling and a stimuli response that show promise in applications ranging from drug delivery to water remediation.

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.

Aquatic Functional Liquid Crystals: Design, Functionalization, and Molecular Simulation.

Aquatic functional liquid crystals, which are ordered molecular assemblies that work in water environment, are described in this review. Aquatic functional liquid crystals are liquid-crystalline (LC) materials interacting water molecules or aquatic environment. They include aquatic lyotropic liquid crystals and LC based materials that have aquatic interfaces, for example, nanoporous water treatment membranes that are solids preserving LC order. They can remove ions and viruses with nano- and subnano-porous structures. Columnar, smectic, bicontinuous LC structures are used for fabrication of these 1D, 2D, 3D materials. Design and functionalization of aquatic LC sensors based on aqueous/LC interfaces are also described. The ordering transitions of liquid crystals induced by molecular recognition at the aqueous interfaces provide distinct optical responses. Molecular orientation and dynamic behavior of these aquatic functional LC materials are studied by molecular dynamics simulations. The molecular interactions of LC materials and water are key of these investigations. New insights into aquatic functional LC materials contribute to the fields of environment, healthcare, and biotechnology.

Antimicrobial peptide dendrimers assisted Nanocomposite-Loaded lyotropic liquid crystalline for multimodal surgical site infection management

Superficial incisional surgical site infections (SISSIs) were a serious challenge leading to delayed wound healing and even systemic diseases. The high incidence of antibiotic resistance and unprotected wound lesions severely hindered the current therapeutical efficiency. In this study, an antibacterial nanocomposite PAMAM-PLL@AuNPs was designed to avoid antibiotic resistance, and a lyotropic liquid crystal system was used for local drug delivery and protecting lesions. The PAMAM-PLL was constructed with polyamide amine (PAMAM) as the core and polylysine (PLL) as the branch chain, which increased the antibacterial activity by 4 times. After being connected to gold nanoparticles (AuNPs), a further 2 times antibacterial activity improvement was achieved. PAMAM-PLL@AuNPs could eliminate bacteria by multimodal mechanisms, including causing leakage of intracellular substances, inducing intracellular reactive oxygen species and inhibiting bacterial metabolism. Thanks to their spontaneous phase transition and the mechanical response characteristics of the lattice structure, lyotropic liquid crystal with self-healing characteristics was employed to load PAMAM-PLL@AuNPs. The unique structure facilitated buffering external forces and accelerated wound healing. The excellent antibacterial and wound healing properties of the lyotropic liquid crystal drug delivery system were confirmed by a surgical incision infection model. This study is expected to provide a robust strategy for the treatment of SISSIs.

Understanding the role of water in the lyotropic liquid crystalline mesophase of high-performance flexible supercapacitor electrolytes using a rheological approach

The effect of water on the structure, properties, and flexibility of lyotropic liquid crystalline (LLC) C12E23-LiCl-H2O gel electrolytes was explored. Structural techniques, such as X-ray Diffraction (XRD), Polarized Optical Microscopy (POM), and five dynamic measurements, were employed to examine the rheological properties of the LLC mesophase across various water contents. These analyses provided quantitative insights into the influence of water content and LiCl concentration on gel strength, gelation point, and structural recovery. The three-dimensional network of the gel encapsulates Li+ and Cl− ions within hydrophilic domains, showing significant performance in supercapacitor applications. The observed increase in storage modules with decreasing water content is attributed to variations in the quantity and average size of junction points owing to system entanglement. These research findings highlight that excess water molecules, which break down micellar connections, are responsible for the weakening of the gel. Conversely, at low water concentrations, the micellar domains entangle, displaying viscoelastic behavior akin to that of a transitory polymer network.

Intrinsic and Dynamic Heterogeneity of Nonlamellar Lyotropic Liquid Crystalline Nanodispersions.

Nonlamellar lyotropic liquid crystalline (LLC) nanoparticles are a family of versatile nano-self-assemblies, which are finding increasing applications in drug solubilization and targeted drug delivery. LLC nanodispersions are heterogeneous with discrete nanoparticle subpopulations of distinct internal architecture and morphology, frequently coexisting with micelles and/or vesicles. Diversity in the internal architectural repertoire of LLC nanodispersions grants versatility in drug solubilization, encapsulation, and release rate. However, drug incorporation contributes to the heterogeneity of LLC nanodispersions, and on exposure to biological media, LLC nanodispersions often undergo nanostructural and morphological transformations. From a pharmaceutical perspective, coexistence of multiple types of nanoparticles with diverse structural attributes, together with media-driven transformations in colloidal characteristics, brings challenges in dissecting biological and therapeutic performance of LLC nanodispersions in a spatiotemporal manner. Here, we outline innate and acquired heterogeneity of LLC nanodispersions and discuss technological developments and alternative approaches needed to improve homogeneity of LLC formulations for drug delivery applications.

Phase Behavior and Structure of Poloxamer Block Copolymers in Protic and Aprotic Ionic Liquids.

Ionic liquids are promising media for self-assembling block copolymers in applications such as energy storage. A robust design of block copolymer formulations in ionic liquids requires fundamental knowledge of their self-organization at the nanoscale. To this end, here, we focus on modeling two-component systems comprising a Poly(ethylene oxide)-poly (propylene oxide)-Poly(ethylene oxide) (PEO-PPO-PEO) block copolymer (Pluronic P105: EO37PO58EO37) and room temperature ionic liquids (RTILs): protic ethylammonium nitrate (EAN), aprotic ionic liquids (1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6), or 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF4). Rich structural polymorphism was exhibited, including phases of micellar (sphere) cubic, hexagonal (cylinder), bicontinuous cubic, and lamellar (bilayer) lyotropic liquid crystalline (LLC) ordered structures in addition to solution regions. The characteristic scales of the structural lengths were obtained using small-angle X-ray scattering (SAXS) data analysis. On the basis of phase behavior and structure, the effects of the ionic liquid solvent on block copolymer organization were assessed and contrasted to those of molecular solvents, such as water and formamide.

The influence of mannose-based esters on the mesophase behaviour of lyotropic liquid crystalline nanosystems as drug delivery vectors

Lyotropic Liquid Crystalline (LLC) nanoparticles represent an emerging class of smart, biocompatible, and biodegradable systems for the delivery of drugs. Among these, structures with complex 3D architectures such as cubosomes are of particular interest. These are non- lamellar assemblies having hydrophobic and hydrophilic portions able to carry drugs of different nature. They can further be modulated including suitable additives to control the release of the active payload, and to promote an active targeting. Starting from monoolein (GMO) cubic phase, different concentrations of mannose-based esters were added, and the eventual structural modifications were monitored to ascertain the effects of the presence of glycolipids. Moreover, the structural properties of these nanosystems loaded with Dexamethasone (DEX), a very well-known anti-inflammatory steroid, were also studied. Experiments were carried out by synchrotron Small Angle X-ray Scattering (SAXS), Raman Microspectroscopy (RMS) and Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) measurements. The drug delivery potential (i.e. entrapment efficiency and release properties) of the obtained nanoparticles was evaluated. Finally, in vitro cytocompatibility and anti-inflammatory activity studies of the prepared formulations were carried out. Inclusion of mannose-based surfactants up to 10 mol% influenced the structural parameters of Im3m cubic phase and swollen cubic phases were obtained with the different glycolipids with lattice parameters significantly higher than GMO. A complete cytocompatibility and an increased DEX activity were observed, thus suggesting the possibility to use GMO/glycolipids nanoparticles to formulate innovative drug delivery systems.

Residual‐Chemical‐Shift‐Anisotropy‐Based Enantiodifferentiation in Lyotropic Liquid Crystalline Phases Based on Helically Chiral Polyacetylenes

AbstractAnisotropic NMR spectroscopy, revealing residual dipolar couplings (RDCs) and residual chemical shift anisotropies (RCSAs) has emerged as a powerful tool to determine the configurations of synthetic and complex natural compounds. The deduction of the absolute in addition to the relative configuration is one of the primary goals in the field. Therefore, the investigation of the enantiodiscriminating capabilities of chiral alignment media becomes essential. While RDCs and RCSAs are now used for the determination of the relative configuration routinely, RCSAs have not been measured in chiral alignment media such as chiral liquid crystals. Herein, we present this application by measuring RCSAs for chiral analytes such as indanol and isopinocampheol in the lyotropic liquid crystalline phase of an L‐valine derived helically chiral polyacetylenes. We have also demonstrated that a single 1D 13C−{1H} NMR spectrum suffices to get the RCSAs circumventing the necessity to acquire two spectra at two alignment conditions.

Residual-Chemical-Shift-Anisotropy-Based Enantiodifferentiation in Lyotropic Liquid Crystalline Phases Based on Helically Chiral Polyacetylenes.

Anisotropic NMR spectroscopy, revealing residual dipolar couplings (RDCs) and residual chemical shift anisotropies (RCSAs) has emerged as a powerful tool to determine the configurations of synthetic and complex natural compounds. The deduction of the absolute in addition to the relative configuration is one of the primary goals in the field. Therefore, the investigation of the enantiodiscriminating capabilities of chiral alignment media becomes essential. While RDCs and RCSAs are now used for the determination of the relative configuration routinely, RCSAs have not been measured in chiral alignment media such as chiral liquid crystals. Herein, we present this application by measuring RCSAs for chiral analytes such as indanol and isopinocampheol in the lyotropic liquid crystalline phase of an L-valine derived helically chiral polyacetylenes. We have also demonstrated that a single 1D 13 C-{1 H} NMR spectrum suffices to get the RCSAs circumventing the necessity to acquire two spectra at two alignment conditions.