Liquid Crystalline Matrix Research Articles

Lipid-based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water-soluble drugs: cellular interaction and in vivo absorption

BackgroundLipid-based liquid crystalline nanoparticles (LCNPs) have attracted growing interest as novel drug-delivery systems for improving the bioavailability of both hydrophilic and hydrophobic drugs. However, their cellular interaction and in vivo behavior have not been fully developed and characterized.MethodsIn this study, self-assembled LCNPs prepared from soy phosphatidylcholine and glycerol dioleate were developed as a platform for oral delivery of paclitaxel. The particle size of empty LCNPs and paclitaxel-loaded LCNPs was around 80 nm. The phase behavior of the liquid crystalline matrix was characterized using crossed polarized light microscopy and small-angle X-ray scattering, and showed both reversed cubic and hexagonal phase in the liquid crystalline matrix. Transmission electron microscopy and cryofield emission scanning electron microscopy analysis revealed an inner winding water channel in LCNPs and a “ ball-like”/“hexagonal” morphology.ResultsCellular uptake of LCNPs in Caco-2 cells was found to be concentration-dependent and time-dependent, with involvement of both clathrin and caveolae/lipid raft-mediated endocytosis. Under confocal laser scanning microscopy, soy phosphatidylcholine was observed to segregate from the internalized LCNPs and to fuse with the cell membrane. An in vivo pharmacokinetic study showed that the oral bioavailability of paclitaxel-loaded LCNPs (13.16%) was 2.1 times that of Taxol® (the commercial formulation of paclitaxel, 6.39%).ConclusionThe findings of this study suggest that this LCNP delivery system may be a promising candidate for improving the oral bioavailability of poorly water-soluble agents.

Liquid crystalline nanostructures: organizing matrices for non-enzymatic nucleic acid polymerization

When a mixture of amphiphilic compounds and solute molecules undergoes dehydration, a liquid crystalline multilamellar matrix is produced that organizes and concentrates solute molecules between lamellae. If the solutes are nucleotides, RNA-like molecules can be synthesized by a condensation reaction when the system is exposed to one or more cycles of dehydration at elevated temperatures, followed by rehydration. The chemical potential driving the reaction is supplied by the anhydrous conditions in which water becomes a leaving group, with heat providing activation energy. Liquid crystalline matrices composed of amphiphilic compounds could have promoted polymerization reactions in prebiotic conditions, giving rise to the molecular complexity required for the origin of cellular life.

Nano-biphasic ionic liquid systems composed of hydrophobic phosphonium salts and a hydrophilic ammonium salt

A combination of a phosphonium-type-zwitterions-lithium bis(trifluoromethanesulfonyl)imide complex and a hydrophilic ammonium salt provides a nanosegregated liquid-crystalline matrix consisting of hydrophilic ionic liquid (IL) domains and hydrophobic IL domains.

Liquid-Crystalline Polymer Composites with CdS Nanorods: Structure and Optical Properties

We report on the structure, uniaxial orientation, and photoluminescent properties of CdS nanorods that form stable nanocomposites with smectic C hydrogen-bonded polymers from the family of poly(4-(n-acryloyloxyalkoxy)benzoic acids. TEM analysis of microtomed films of nanocomposites reveals that CdS nanorods form small domains that are homogeneously distributed in the LC polymer matrix. They undergo long-range orientation with the formation of one-dimensional aggregates of rods when the composite films are uniaxially deformed. The Stokes photoluminescence was observed from CdS NRs/LC polymer composites with emission peak located almost at the same wavelength as that of NRs solution in heptane. An anti-Stokes photoluminescence (ASPL) in polymer nanocomposites was found under the excitation below the nanoparticles ground state. The mechanism of ASPL was interpreted in terms of thermally populated states that are involved in the excitation process. These nanocomposites represent an unusual material in which the optical properties of anisotropic semiconductor nanostructures can be controlled by mechanical deformation of liquid-crystalline matrix.

Eu(III)-coupled luminescent multi-walled carbon nanotubes in surfactant solutions

A carbon nanotube/inorganic hybrid material has been fabricated by coupling Eu(III) complexes onto multi-walled carbon nanotubes (MWCNTs). Successful coupling has been verified by X-ray photoelectron spectroscopy (XPS) measurement where a clear signal from Eu3d has been identified. When sonicated in hexaethylene glycol monododecyl ether (C 12E 6) or sodium dodecyl sulfate (SDS) aqueous solutions, the MWCNTs with Eu-complex attached (denoted as Eu-MWCNTs hereafter) can be dispersed. UV–vis measurements on a dilute dispersion of Eu-MWCNTs in SDS aqueous solution reveal the characteristic absorption from Eu(III) complexes, which gives further proof of the successful coupling. The strong luminescent properties of Eu-MWCNTs allow them to be observed directly under a fluorescence microscope. Interestingly, it is found that Eu-MWCNTs can undergo continuous movements in C 12E 6 or SDS dilute solutions. When Eu-MWCNTs are incorporated into the lyotropic liquid crystal phase formed by C 12E 6 (above 40% by weight), however, movements have been hindered. Small angle X-ray scattering measurements showed that Eu-MWCNTs are ordered in the lyotropic liquid crystal. Fluorescence microscopy observations reveal that the luminescent properties of the Eu-MWCNTs have not been affected by the liquid crystalline surfactant matrix.

Tailoring Crystallization Behavior of PEO-Based Liquid Crystalline Block Copolymers through Variation in Liquid Crystalline Content

A series of liquid crystalline–semicrystalline–liquid crystalline triblock copolymers, with poly(ethylene oxide) (PEO) as the semicrystalline central block and polymethacrylate bearing side-chain cholesteryl mesogens as the liquid crystalline (LC) end blocks, are prepared using reversible addition–fragmentation chain transfer (RAFT) polymerization. Starting with 20 kg/mol PEO, the weight fractions of the LC blocks in the triblock copolymers are varied from 21 to 86 wt %. The wide-angle and small-angle X-ray scattering (WAXS and SAXS) as well as transmission electron microscopy (TEM) studies show that with the increased LC content in the triblock copolymers different hierarchical structures including “LC lamellae in PEO lamellae” and “PEO cylinders in LC matrix” are observed sequentially. Differential scanning calorimetry (DSC) study shows that the triblock copolymers with “LC lamellae in PEO lamellae” crystallize at normal undercooling conditions (crystallization temperature Tc observed at 31.0–36.4 °C, which is close to that of homopolymer PEO), while those with “PEO cylinders in LC matrix” crystallize at very large undercooling (Tc drops to −23.5 to −27.8 °C). The large variation of the undercooling conditions required for PEO crystallization is attributed to the nanoconfinement effect from different hierarchical structures at varied LC contents. Avrami analysis has been performed to understand the PEO crystallization mechanism. In “LC lamellae in PEO lamellae”, the PEO crystallization is confined within 2D microdomains between LC lamellae and follows heterogeneous nucleation mechanism with subsequent long-range crystal growth. In “PEO cylinders in LC matrix”, the PEO crystallization is confined within 1D cylindrical microdomains and dominated by homogeneous nucleation, and long-range crystal growth is prohibited by the surrounding LC matrix. This study demonstrates that microsegregated LC domains can provide efficient confinement of the PEO crystallization, and by simply increasing the LC content, amorphous PEO can be obtained at room temperature. These LC–semicrystalline–LC triblock copolymers, with room temperature amorphous PEO confined in microsegregated nanodomains, may be used as scaffolds for lithium ion batteries and solid-state electrolytes.

Opto‐Mechanical Effect in Photoactive Nematic Side‐Chain Liquid‐Crystalline Elastomers

The mechanical behaviour of monodomain nematic side-chain liquid-crystalline elastomers containing azoderivatives as pendant groups or crosslinkers has been studied under UV irradiation and in the darkness at different temperatures. From the evaluation of the opto-mechanical experiments, the mechanical efficiency, kinetic rates, activation energies and the isomerization mechanism of the azocompounds in the liquid-crystalline matrix could be determined, as well as the effect of the chemical constitution of the azobenzene derivatives and their role in the elastomeric network.

Carbon Nanotubes Chemically Derivatized with Redox Systems as Mediators for Biofuel Cell Applications

The aim of this study was designing of nanostructured bioelectrodes and assembling them into a biofuel cell with no separating membrane. Carbon nanotubes (CNTs) chemically connected with residues of typical mediators, i.e. ferrocene (Fc) and 2,2′-azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) deposited on glassy carbon electrodes (GCE) were found useful as mediators for the enzyme catalyzed electrode processes. The electrodes were in turn covered with glucose oxidase from Aspergillus niger AM-11 and laccase from Cerrena unicolor C-139, respectively, incorporated in a liquid-crystalline matrix. The nanostructured electrode coating with the cubic phase film containing enzymes acted as the catalytic surface for the enzymatic reactions that is oxidation of glucose at anode and reduction of oxygen at cathode. For the system with mediators anchored to CNTs the catalysis was almost ten times more efficient than on bare GCE electrodes: catalytic current of glucose oxidation was 1 mAcm–2 and oxygen reduction current exceeded 0.6 mAcm–2. The open circuit voltage of the biofuel cell was 0.43 V. Application of the carbon nanotubes increased maximum power output of the constructed biofuel cell to 100 μWcm–2 without stirring the solution. It is ca. 100 times more efficient than using the same bioelectrodes without nanotubes on the electrode surface.

Investigation of the mechanical properties of a low-shrinkage liquid crystalline matrix combined with nano-hydroxyapatite

The objective of this study was to investigate the mechanical properties of a low-shrinkage acrylate liquid crystalline resin matrix (ALCRM), (4-3-(acryloyloxy)-2-hydroxypropoxy) phenyl 4-(3-(acryloyloxy)-2-hydroxypropoxy) benzoate, combined with nano-hydroxyapatite (na-HA). The ALCRM monomer and diluent monomer triethylene glycol dimethacrylate (TEGDMA) were mixed at a mass ratio of 7:3 to prepare the resin matrix. The volume shrinkage of the ALCRM/TEGDMA and the traditional resin matrix Bis-GMA (2, 2-bis [4-(3-methacryloxy-2-hydroxypropoxy) phenyl] propane)/TEGDMA were measured. Then 20%, 30%, and 40% na-HA were added to ALCRM/TEGDMA and Bis-GMA/TEGDMA, respectively. Compressive strength (CS) and Vickers hardness (VHN) were tested to identify mechanical properties of the composites. The volume shrinkage of the ALCRM/TEGDMA was 3.60% ± 0.36%, which was lower than that of the traditional resin matrix. Moreover, with the same amount of na-HA filler, the mechanical properties of the ALCRM-based composites were superior to those of Bis-GMA-based composites. ALCRM-based composites exhibited the highest CS and VHN values when the filler content was 30%. These results indicate that the low-shrinkage liquid crystalline resin matrix has strong mechanical properties after incorporating the na-HA. The experimental ALCRM-based composites have promising potential for the development of novel low-shrinkage dental resins with strong mechanical properties.

Reversible projective measurement in quantum ensembles

We present experimental NMR demonstration of a scheme of reversible projective measurement, which allows extracting information on outcomes and probabilities of a projective measurement in a non-destructive way, with a minimal net effect on the quantum state of an ensemble. The scheme uses reversible dynamics and weak measurement of the intermediate state. The experimental system is an ensemble of 133Cs (S = 7/2) nuclei in a liquid-crystalline matrix.

Ordering dynamics of blue phases entails kinetic stabilization of amorphous networks

The cubic blue phases of liquid crystals are fascinating and technologically promising examples of hierarchically structured soft materials, comprising ordered networks of defect lines (disclinations) within a liquid crystalline matrix. We present large-scale simulations of their domain growth, starting from a blue phase nucleus within a supercooled isotropic or cholesteric background. The nucleated phase is thermodynamically stable; one expects its slow orderly growth, creating a bulk cubic phase. Instead, we find that the strong propensity to form disclinations drives the rapid disorderly growth of a metastable amorphous defect network. During this process, the original nucleus is destroyed; reemergence of the stable phase may therefore require a second nucleation step. Our findings suggest that blue phases exhibit hierarchical behavior in their ordering dynamics, to match the hierarchy in their structure.

LIQUID CRYSTALLINE WATER, QUANTUM MOLECULAR MACHINES & THE LIVING STATE

It has been 18 years since the discovery in my laboratory suggesting that living organisms are dynamic liquid crystalline phases in which all the molecules in the cells and tissues of the body are aligned and moving coherently together, including especi- ally the water molecules that are intrinsic to the liquid crystalline matrix and essential to the function of macromolecules. In effect, the organism depends on a macroscopic quantum co- herence of individual molecular energy machines. Recent investigations using a range of sophisticated spectroscopic techniques have indeed revealed that the liquid crystalline (hydration) water forms dynamically coherent units with proteins and nucleic acids, and enables the macromolecules to function cohe- rently together. The same investigations also reveal that ions play their pivotal role in cellular meta- bolism and signalling through interactions with hydration water. Despite these major advances, the ultimate mystery of life remains tantalizingly beyond our grasp. Keywords: liquid crystalline organism, quantum coherence, molecular energy mac- hines, hydration water, two-states water, kosmotrope and chaotrope, Law of matching water affinities, microdomains.

Phytantriol and glyceryl monooleate cubic liquid crystalline phases as sustained-release oral drug delivery systems for poorly water-soluble drugs II. In-vivo evaluation

Abstract Objectives Lipid-based liquid crystals formed from phytantriol (PHY) and glyceryl monooleate (GMO) retain their cubic-phase structure on dilution in physiologically relevant simulated gastrointestinal media, suggesting their potential application as sustained-release drug-delivery systems for poorly water-soluble drugs. In this study the potential of PHY and GMO to serve as sustained-release lipid vehicles for a model poorly-water-soluble drug, cinnarizine, was assessed and compared to that of an aqueous suspension formulation. Methods Small-angle X-ray scattering was used to confirm the nanostructure of the liquid-crystalline matrix in the presence of the selected model drug, cinnarizine. Oral bioavailability studies were conducted in rats, and disposition of lipid and drug in segments of the gastrointestinal tract was determined over time. Differences in the digestibility and stability of formulations under digestion conditions were investigated using an in-vitro lipolysis model. Key findings The oral bioavailability of cinnarizine using the PHY formulation was 41%, compared to 19% for the GMO formulation and 6% for an aqueous suspension. The PHY formulation provided a Tmax for cinnarizine of 33 h, with absorption apparent up to 55 h after administration. In contrast, the Tmax for the GMO formulation was only 5 h. The PHY formulation was retained in the stomach for extended periods of time, with 56% of lipid remaining in the stomach after 24 h, in contrast to less than 1% of the GMO formulation after 8 h, suggesting that gastric retention was a key aspect of the prolonged period of absorption, which correlated with the formulations' relative susceptibility to in-vitro lipolysis and degradation. Conclusions PHY provides a dramatic sustained-release effect for cinnarizine on oral administration, which is linked to gastric retention of the formulation and its ability to resist digestive processing. Poorly digested liquid crystal lipid formulations therefore offer a novel class of sustained-release matrices for oral administration.

Electro-optical modulators in polymer-dispersed liquid crystal complexes

The influence of bicolor optical treatment on the behaviour of the linear and quadratic electro-optical effects in the LCBO NC incorporated into the liquid crystalline matrix is studied. Simultaneously their dependence on frequency is analyzed. With increasing power density up to 250–270 MW/cm 2 there is a substantial increase of the electro-optical coefficient at 1150 nm up to 1.75 pm/V and 1.53 pm/V for 5% and 3% LCBO nanocrystallites, respectively. Further enhancement of the photo-inducing treatment leads to a saturation of the process. The behaviour of the maximal quadratic electro-optics coefficient R 2233 demonstrates principally different photo-inducing dependences. For both LCBO contents we observe an occurrence of the maximum in the electro-optical coefficients situated at 120 and 180 MW/cm 2 powers for the fundamental laser beams. However, contrary to the Pockels effect the enhanced content of the LCBO NC leads to a decrease of the observed effect.

CaCO3/chitin-whisker hybrids: formation of CaCO3 crystals in chitin-based liquid-crystalline suspension

CaCO3/chitin-whisker hybrids were prepared using the liquid-crystalline suspension of the chitin whisker. Suspensions of chitin nanowhiskers were obtained by acid hydrolysis of chitin powder. The suspension containing about 5 wt% of whiskers exhibited lyotropic liquid-crystalline behavior. The suspension was converted to a gel form when it was exposed to ammonium carbonate vapor. CaCO3 crystals were formed for 30 days in chitin gels as templates. The nucleation of CaCO3 occurred in the liquid-crystalline chitin matrix and the CaCO3 crystals deposited in the chitin gels to form hybrids with an interpenetrated three-dimensional structure. Scanning electron microscopy image of the fractured sample of the hybrid showed that the gel matrix was filled with CaCO3 crystals. Thermogravimetric analysis revealed that the composition of CaCO3/polymer/H2O is about 2:6:2 in weight. This approach inspired by biomineralization may be useful for the development of inorganic/organic hybrid materials. CaCO3/chitin-whisker hybrids were prepared by deposition of CaCO3 crystals in ordered chitin gel matrices. The gels were prepared by conversion of lyotropic liquid crystals of chitin whiskers.

AFM surface morphology and friction force studies of microscale domain structures of binary phospholipids

We have studied friction forces on binary mixtures of phospholipid monolayer films. The phospholipid monolayer films have been prepared via the Langmuir–Blodgett (LB) technique on mica. The two-component phospholipids are distearoylphosphatidylcholine (DSPC) and dilauroylphosphatidylcholine (DLPC). At 25 °C the LB monolayer films give the gel-state DSPC domains surrounded by the liquid crystalline DLPC matrix. The friction forces measured on the DSPC domain region are significantly greater than those on the DLPC matrix region at this temperature. An increased temperature results in a decreased friction of the DSPC domain region, and above the gel-to-liquid crystalline phase transition temperature of DSPC, the difference in the friction forces measured on the two phospholipids becomes negligible. This means that the phase state is a key factor in determining friction forces on the phospholipid monolayer films.

Surfactant systems for nasal zidovudine delivery: structural, rheological and mucoadhesive properties

Zidovudine is the antiretroviral drug most frequently used for the treatment of AIDS. Although its effectiveness is recognized, it undergoes extensive first-pass metabolism and exhibits poor oral bioavailability. The nasal route is an option for enhanced therapeutic efficacy and to reduce the extent of the first-pass effect. There are some mechanisms that limit intranasal absorption, such as mucociliary clearance, which rapidly removes the formulation from the nasal cavity. To improve the nasal residence time of zidovudine on the nasal mucosa, we aimed to develop a mucoadhesive surfactant system for zidovudine nasal administration. Systems composed of PPG-5-CETETH-20 as surfactant, oleic acid and water were characterized by polarized light microscopy, small-angle X-ray scattering and rheological measurements. Mucoadhesion was investigated by phase behaviour studies, rheological synergism and mucoadhesive strength determination. Results indicate that the original formulations were microemulsions that displayed phase transition to a lamellar phase when brought into contact with aqueous nasal simulated mucus. The phase transition was accompanied by an increase in system elasticity and, irrespective of phase behaviour, all the systems showed a good mucoadhesive force. Thus, a viscous and mucoadhesive liquid crystalline matrix could be formed when the formulations were in contact with simulated mucus, which may prolong the residence time of zidovudine in the nasal cavity. These findings indicate a potentially useful system for nasal administration of zidovudine.

Extension rheology of liquid-crystalline solution/layered silicate hybrids

The extension rheology of polymer/layered silicate composites based on liquid-crystalline (LC) solution of hydroxypropylcellulose (HPC) in oligomeric polyethyleneglycole (PEG) was studied. The HPC concentration was 60 wt%. Extension experiments have been carried out for materials in the different phase states. Compositions containing Na-montmorillonite (MMT) were prepared by a two-stage method. Final systems may be attributed to solutions of HPC in PEG, which intercalates into MMT galleries. The ordered domain structure of the LC matrix as well as hydrogen-bonded network between HPC and PEG molecules significantly reduce deformation at break and provide a strong nonlinear viscoelastic behavior at extension. Appearance of isotropic phase in solutions leads to a sharp drop of the elongation viscosity. The introduction of clay into LC solution only slightly affects the viscosity value but significantly suppresses the strain-hardening scale. In contrast, loading in biphasic state of HPC-PEG solution with even small amount (1 wt%) of MMT leads to the drastic viscosity increase that does not change in further growth of the filler concentration. Elastic properties of the systems under study demonstrate the similar behavior. This effect likely is caused by the interrelationship between deformability of the LC domain structure and the network strength formed by the clay particles. POLYM. ENG. SCI., 2010. © 2009 Society of Plastics Engineers

Self-Assembled Superlattices of Gold Nanoparticles in a Discotic Liquid Crystal

There is considerable interest in the inclusion of functionalised nanoparticles in discotic liquid crystals as they exhibit interesting self-assembled structures and electronic properties. In this view, we have carried out magnetic susceptibility, DC conductivity and small angle X-ray diffraction studies (SAXS) on hexanethiol covered gold nanoparticles (GNPs) in a discotic liquid crystal namely hexahexylthiotripheneylene (HHTT). Our SAXS pattern for the pure HHTT in the helical columnar liquid crystalline phase (H) showed a sharp peak corresponding to the intercolumnar spacing between the discotic columns. On the other hand, our SAXS pattern for the GNPs:HHTT (1:4 wt%) in the H phase of the composite showed a broad peak. The broad peak exhibits shoulders indicating additional peaks and they can be indexed to 2D hexagonal superlattices. Our room temperature transmission electron microscope (TEM) image of the pure hexanethiol covered gold nanoparticles showed predominantly 1.2 nm diameter GNPs along with a small number of 2.6 nm and 4.6 nm GNPs. From our studies, we infer that the smaller 1.2 nm GNPs randomly occupy positions in the liquid crystalline matrix within the columns as well as in between the columns. The bigger nanoparticles (2.6 nm and 4.6 nm) form 2D intercalated hexagonal structure with the disc molecules. We find about two to three orders of increase in the DC conductivity in the isotropic and mesophases with respect to those of the pure HHTT. We attribute this increase mainly to the insertion of 1.2 nm GNPs in the columns. We also find further increase in the conductivity by some three orders of magnitude in the crystalline phase of the composite with respect to its higher temperature phases. Magnetic susceptibility studies also showed a discontinuous change near the crystallization temperature. Enhanced core-core ordering in the crystalline phase of the composite with respect to its higher temperature phases may be responsible for these observations.

Macroscopic-scale carbon nanotube alignment via self-assembly in lyotropic liquid crystals

By dispersing carbon nanotubes (CNTs) in a lyotropic liquid crystalline matrix, uniaxial alignment of the nanotubes can easily be achieved over macroscopic areas. We briefly describe the principles behind the technique and then show that it can be applied to multiwall as well as single-wall nanotubes and that a variety of different dispersing materials can be used, from industrial surfactants to DNA. We also present a new microfluidics-based method for transferring the liquid crystal-dispersed CNTs to a substrate, maintaining a fair control of tube direction.