Lyotropic Liquid Crystalline Structures Research Articles

Chelating phytanyl-EDTA amphiphiles: self-assembly and promise as contrast agents for medical imaging

Chelating amphiphiles of ethylene diamine tetraacetic acid (EDTA) have been synthesized by conjugation to one or two C20 isoprenoid-type chain/s (phytanyl) via an ester bond. EDTA-mono and bis phytanyl (EDTA-MP and EDTA-BP) have the ability to sequester a variety of metal ions, including transition metal ions and paramagnetic metal ions such as manganese (Mn) and gadolinium (Gd). Both amphiphiles and their metal complexes were examined for ordered self-assembled structures in the solid state and as hydrated lyotropic liquid crystalline phases. For the neat materials small and wide angle X-ray scattering (SAXS/WAXS) revealed lamellar structures with molten hydrophobic chains for the mono-phytanyl conjugate, however, neither Gd-EDTA-MP nor Mn-EDTA-MP showed any ordered phases. The bis-phytanyl conjugate displayed a less ordered structure, while its Mn complexed conjugate demonstrated an ordered lamellar phase with molten chains. Lyotropic liquid crystalline structures of these amphiphiles were examined by cross polarizing optical microscopy (POM) and SAXS methods in the presence of water or sodium acetate solution (100 mM, 200 mM, 500 mM and 1 M). EDTA-MP formed a lamellar liquid crystal (Lα), whilst higher order inverse hexagonal (HII) and micellar cubic phases (III) with Fd3m symmetry were displayed by the bis- conjugate. Dispersions of these amphiphiles buffered in sodium acetate solution yielded submicron sized particles with analogous nanostructures (liposomes, hexosomes), which were examined by Synchrotron SAXS and visualized with Cryo-TEM. The influence of pH upon the morphology of the nanostructures was critical, with hexosomes of EDTA-BP (pH = 5.7) converting to liposomes at pH > 6. Dispersed Mn and Gd complexed particles were examined as contrast agents (CAs) for magnetic resonance imaging by low field NMR measurements. Mn and Gd complexed nanostructured particles displayed improved relaxivity over Mn-EDTA and Gd-EDTA, respectively. The formation of highly ordered nanostructured self-assembly materials by these chelating amphiphiles combined with their ability to sequester a variety of metal ions, including paramagnetic metal ions, suggests their potential application as contrast agents for MRI.

Lyotropic Phase Behavior of Poly(ethylene oxide)−Poly(butadiene) Diblock Copolymers: Evolution of the Random Network Morphology

The phase behavior of poly(ethylene oxide)−poly(butadiene) (PEO-PB) diblock copolymers mixed with water was studied using small-angle X-ray scattering (SAXS), cryogenic scanning electron microscopy (cryo-SEM), cryogenic transmission electron microscopy (cryo-TEM), and dynamic mechanical spectroscopy. Two sets of diblocks were synthesized by adding different lengths of PEO to hydroxy terminated PB with degrees of polymerization NPB = 46 and 170. Two-component mixtures were investigated as a function of block composition and copolymer molecular weight, between 1 and 100 wt % polymer content. Melt phase behavior is consistent with established theory and known experimental behavior for diblock copolymers. Various lyotropic liquid crystalline structures, notably lamellae (L), hexagonally packed cylinders (H), and spheres (S) arranged on cubic (body-centered cubic, face-centered cubic) lattices, were documented as a function of water content. At the higher molecular weights (NPB = 170), a random network phase (N) was identified over a sizable portion of the phase portrait, located between hexagonally ordered cylinders and ordered lamellae. This new structure, along with branching of cylindrical micelles in the dilute limit, bear a striking similarity to experimentally observed and theoretically predicted phase behavior in certain ternary water/oil/surfactant systems. These findings demonstrate that block copolymer surfactants are characterized by at least four structural building blocks—spheres, cylinders, bilayers, and branched cylinders—above a threshold molecular weight.

On structural transitions in a discontinuous micellar cubic phase loaded with sodium diclofenac

An intermediate mesophase of lyotropic liquid crystalline structure from the ternary mixtures of glycerol monooleate, water, and ethanol was recently characterized in our lab. This mesophase, termed Q L , consists of discrete discontinuous micelles arranged in a cubic array. The Q L phase can solubilize very significant loads of water-insoluble anti-inflamatory drug sodium diclofenac (Na-DFC). Close examination of the internal structures of the lyotropic liquid structure upon increasing the solubilization loads reveals the existence of three structural transitions controlled by the Na-DFC levels. Up to 0.4 wt% Na-DFC, the Q L structure remains intact with some influence on the hydration of the headgroups and on the intermicellar forces. However, at 0.8 to 1.2 wt% Na-DFC, the discontinuous micellar cubic phase is transformed into a more condensed mesophase of a bicontinuous cubic phase. At > 1.2 wt% Na-DFC, the cubic phase is converted into a lamellar phase ( L α ). Within 5.5 to 7.3 wt% Na-DFC the mesophase is progressively transformed into a less ordered lamellar structure. At ⩾ 12 wt% Na-DFC crystals tend to precipitate out. At low Na-DFC concentrations the drug behaves like a lyotropic or kosmotropic salt and can salt-out the surfactant from its water layer, but at higher levels it behaves like a hydrotropic, chaotropic salt and can salt-in the surfactant. The Na-DFC location and position within the interface as well as its polarization and partial ionization are strongly affected by its solubilization contents and the structure that it is inducing. In the cubic phase the drug is located less close to the hydration layer while once transition occurs it is exposed more to the water layer and the surfactant headgroups.

Drying of Films Formed by Ordered Poly(ethylene oxide)−Poly(propylene oxide) Block Copolymer Gels

The drying of hydrogel films formed by poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) block copolymers (Pluronic P105 and Pluronic L64) is investigated at various air relative humidity (RH) conditions in the range 11-94%. These amphiphilic block copolymers self-assemble to form a variety of ordered (lyotropic liquid crystalline) structures as the water content decreases. The amount of water lost increases linearly with the drying time initially (constant rate region, stage I). After this linear region, a falling rate is observed (stage II). The drying rate increases with decreasing RH, thus greatly shortening the drying time. A decrease of the initial film thickness or a decrease in the initial water content shortens the drying time; however, the drying mechanism remains the same. Analysis of the experimental data shows that the hydration level in the Pluronic hydrogel mainly determines the drying rate, rather than the type of ordered structure formed. Two distinct regions (liquid/gel and solid/crystalline) are observed in the drying isotherm for PEO-PPO block copolymers and homopolymer poly(ethylene glycol)s. A model for one-dimensional water diffusion is used to fit the experimental drying results at different RH, initial film thickness, and initial water content conditions. The model accounts for the shrinkage of the film during drying and for a water diffusion coefficient that is a function of the water concentration in the film. For the experimental conditions considered here, the Biot number (Bi) is less than unity and the drying is mainly limited by evaporation at the film surface. The diffusion model is used to obtain information for cases where Bi > 1.

Phase behaviour and structure of amphiphilic poly(ethylene oxide)-poly(propylene oxide) triblock copolymers ((EO)4(PO)59(EO)4 and (EO)17(PO)59(EO)17) in ternary mixtures with water and xylene

The isothermal ternary phase behaviour and structure of amphiphilic copolymer–water–xylene systems was investigated for two poly(ethylene oxide)–poly(propylene oxide) (PEO–PPO) triblock copolymers, (EO)4(PO)59(EO)4 and (EO)17(PO)59(EO)17, at 25°C. The phase boundaries were identified using 2H NMR and inspection under polarized light. The microstructure and structural length scales in the lyotropic liquid crystalline phases were determined and characterized by small-angle X-ray scattering. The amounts and relative proportions of the selective solvents can modulate the resulting microstructures, although the phase sequence observed depends on the relative PEO–PPO block ratio. A variety of lyotropic liquid crystalline (LLC) phases are thermodynamically stable in the system with copolymer (EO)17(PO)59(EO)17, both of the normal ("oil-in-water") and of the reverse ("water-in-oil") morphology. The high hydrophobic content of copolymer (EO)4(PO)59(EO)4, however, favours reverse LLC structures with low interfacial curvature. No normal LLC phases are formed by this system.Key words: amphiphilic, triblock copolymers, poly(ethylene oxide), poly(propylene oxide), ternary mixtures, phase behaviour, lyotropic liquid crystals, SAXS, 2H NMR.

Effect of Pharmaceutically Acceptable Glycols on the Stability of the Liquid Crystalline Gels Formed by Poloxamer 407 in Water

The ability of poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) block copolymers (Poloxamers) to form “gels” (lyotropic liquid crystalline structures) in water is of interest to pharmaceutical applications. In such applications the presence of polar organic solvents is often desirable or required. The effect of such solvents on the stability of lyotropic liquid crystalline gels formed by PEO–PPO–PEO block copolymers was assessed by studying the phase behavior and structure in ternary isothermal (25°C) systems of pharmaceutical interest consisting of Poloxamer 407 (EO 100PO 70EO 100), water, and one of the following solvents (referred to here collectively as “glycols”): glycerol, propylene glycol, ethanol, polyethylene glycol 400, and glucose. Small-angle X-ray scattering was employed to establish the structure of the liquid crystals obtained and to determine their characteristic length scales. The stability range of the liquid crystalline gel phases in the systems studied was found to vary with the glycol type. For example, the micellar cubic structure can accommodate about 0.85 : 1 parts glucose per part water (in terms of weight) and up to as much as 5.5 : 1 parts propylene glycol per part water. A correlation between the glycol effects on the stability of the liquid crystalline phases and glycol physiochemical characteristics such as octanol/water partition coefficient or solubility parameter is proposed.

Lyotropic Liquid Crystalline Structures Formed by Amphiphilic Heteroarm Star Copolymers

Polystyrene/poly(ethylene oxide) heteroarm star copolymers (i.e., star-shaped polymers consisting of a central poly(divinylbenzene) core bearing an equal number of short polystyrene and long poly(ethylene oxide) arms, PS10PEO10) were synthesized by anionic polymerization, and their phase behavior was investigated in aqueous solutions as well as in water−oil solvent mixtures. Because of their amphiphilic character and despite their star architecture, these polymeric species self-assemble under equilibrium conditions into lyotropic liquid crystalline structures.

Interaction of poloxamer block copolymers with cosolvents and surfactants

The interactions of poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) block copolymers (Poloxamers) with cosolvents and surfactants are addressed here. Ternary isothermal (25°C) systems of Pluronic F127 (Poloxamer 407) in the presence of water and polar water-miscible solvents (glycerol, propylene glycol or ethanol), a partially water-miscible solvent (glycerol triacetate), a non-ionic surfactant (tetraethylene glycol monooctyl ether, C 8(EO) 4), an anionic surfactant (sodium dodecyl sulfate, SDS), and a cationic surfactant (cetyltrimethyl ammonium bromide, CTAB) have been investigated by phase behavior studies and small angle x-ray scattering (SAXS). A number of regions with different lyotropic liquid crystalline structure have been identified in each ternary Poloxamer–water–cosolvent/surfactant system. For a given Poloxamer, the composition range over which a given self-assembled structure is stable varies according to the cosolvent/surfactant type (and properties). The effects that the different cosolvents or surfactants exhibit on the Poloxamer phase behavior are interpreted in terms of the preference of the cosolvent/surfactant molecules to locate in different domains of the PEO–PPO–PEO block copolymer self-assembly. Organic solvents, depending on their relative polarities, locate preferably in the PEO-rich or the PPO-rich domains of the microstructure. Some solvents (e.g. ethanol and glycerol triacetate) may show amphiphilic behavior and act as cosurfactants by preferably locating at the interface between the PEO-rich and the PPO-rich domains. The location of the solvents in the block copolymer assemblies is established by an analysis of the trends in the structure lattice spacing (obtained from SAXS) and the interfacial area per block copolymer molecule.

Effect of Glycols on the Self-Assembly of Amphiphilic Block Copolymers in Water. 1. Phase Diagrams and Structure Identification

The effects of cosolvents such as glycerol, propylene glycol, ethanol, or glucose (referred here as “glycols”) on the phase behavior of a representative poly(ethylene oxide)−poly(propylene oxide)−poly(ethylene oxide) (PEO−PPO−PEO) triblock copolymer (Pluronic P105, (EO)37(PO)58(EO)37) are presented. Regions of lamellar, bicontinuous cubic, hexagonal, and micellar cubic lyotropic liquid crystalline structures (established from small-angle X-ray scattering measurements) have been delineated in the four ternary isothermal (25 °C) PEO−PPO−PEO−water−glycol phase diagrams. Pronounced effects on the concentration range of stability of the different phases were found when the glycol was varied from ethanol (the least polar glycol examined here) to glucose (the most polar). For example, glycerol and glucose swell the hexagonal phase to lower copolymer content, while propylene glycol and ethanol do not show this effect. Our experimental observations are discussed in terms of modification of the system “interfacial ...

Phase Behavior and Microstructure in Binary Block Copolymer/Selective Solvent Systems: Experiments and Theory

A combined experimental and theoretical study of phase behavior and structure in binary systems of block copolymers and a selective solvent is presented. The block copolymers used here consist of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), and the solvent is water, selective for the PEO block. The concentration−temperature phase diagrams of (EO)8(PO)47(EO)8 (Pluronic L92) and (EO)11(PO)70(EO)11 (Pluronic L122) in water have been determined experimentally. These two block copolymers are unique in that they form both normal (H1, “oil-in-water”) and reverse (H2, “water-in-oil”) hexagonal lyotropic liquid crystalline structures in binary systems with water over the same temperature range. This is the first time the H2 structure is reported in a binary PEO−PPO−PEO/water system. Thereafter, the predicted phase diagram of (EO)20(PO)69(EO)20 in water is given, employing a self-consistent mean-field lattice theory with internal degrees of freedom. The free energy for a number of possible microstruc...

Liquid crystalline surfactant phases in chemical applications

The importance of lyotropic liquid crystalline structures is shown for two selected surfactant applications,i.e. cosmetics and detergency. The properties of lyotropic liquid crystals are demonstrated for binary surfactant–water systems, ternary surfactant–oil–water systems and multicomponent systems. Detailed knowledge of the phase behavior is crucial for tailor-made product development.

The in vitro release of some antimuscarinic drugs from monoolein/water lyotropic liquid crystalline gels.

To investigate the potential use of a monoolein/water lyotropic liquid crystalline gel for the vaginal delivery of the antimuscarinic drugs, propantheline bromide and oxybutynin hydrochloride to treat urinary incontinence, using Myverol 18-99 as a commercially available grade of monoolein. The influence of propantheline bromide and oxybutynin hydrochloride on the phase structure of Myverol 18-99/water gels was investigated using polarising microscopy. The in-vitro release of the antimuscarinic drugs from Myverol 18-99/water gels was determined and the release pattern interpreted with the aid of results from swelling studies and partition coefficient determinations. Myverol 18-99 forms gels with lyotropic liquid crystalline structures in the presence of water. The addition of propantheline bromide and oxybutynin hydrochloride promoted the formation of gels with a lamellar phase structure. The gels absorbed water at a rate inversely proportional to their initial water content until they reached an equilibrium water content of approximately 40% w/w whilst maintaining their physical integrity. The release of the antimuscarinic drugs was sustained over a period of approximately 18 hours and followed square root of time kinetics indicating that the rate of release was diffusion controlled. The in-vitro release behaviour of Myverol 18-99/water gels suggested that they are suitable carriers to deliver propantheline bromide or oxybutynin hydrochloride. The results of swelling studies indicated that a confined area, such as the vaginal cavity, would be a suitable site of administration.

Lyotropic Liquid Crystalline Structures of Synthetic Polypeptide 2. Measurements of Elastic Constants and Coupling Constants of Poly(γ-Benzyl L-Glutamate) Solutions by the Freedericksz Transition

The object of this report is the determination of material parameters of the lyotropic polymer liquid crystal, poly(γ-benzyl L-glutamate)-1,1,2-trichloroethane solutions, by means of the Freedericksz transition with the magnetic field. The critical field strength Hc of the homeotropic polymer liquid crystal was determined in the condition without hysteresis. The bend elastic constant K33=1.3-1.0×10-11 N and the coupling constant B=4.4×10-6 J m-2 (weight fraction of polymer, w2=0.173 and 0.138) were obtained from the relations between Hc and the cell thickness. The splay elastic constant K11=1.6×10-11 N (w2=0.173 and 0.138) was obtained by the simulations of the transition curves. The ratio K11/K33 exceeds one and is larger than those of the small molecular liquid crystal.

Lyotropic Liquid Crystalline Structures of Synthetic Polypeptides I: Molecular Weight Dependence of the Cholesteric Pitch on Poly(γ-benzyl L-glutamate) Solutions

Abstract A study has been made of the effects of the molecular weight of polymer on the liquid crystalline structures of poly(γ-benzyl L-glutamate) solutions. The cholesteric pitch of poly(γ-benzyl L-glutamate) solution depends on the molecular weight in dioxane and 1,2-dichloroethane (EDC), but is independent of that in dimethyl formamide (DMF). More detailed experiments show that the nematic temperature, at which the cholesteric pitch becomes infinite, varied with molecular weight in dioxane and EDC, but was unchanged in DMF. The relationship between the aggregation states and the molecular weight dependence of the nematic temperature is discussed.

Growth mechanism of myelin figures of phosphatidylcholine

The initial growth process of myelin figures, rod-like lyotropic liquid-crystalline structures, formed by phosphatidylcholine in water, ethylene glycol or glycerin, is suggested to be diffusion-limited with an apparent diffusion coefficient D of approx. 10 −6 cm 2 / s. D can be expressed by the sum of two processes. One is considered to describe the diffusion of an aggregate of phosphatidylcholine molecules and the other mainly to describe a lateral diffusion in the bilayer membranes which constitute myelin figures.

Dielectric properties of microemulsions and of their liquid crystalline mesophases

Isotropic w/o microemulsions as well as the liquid crystalline (LC) phase that develops in the former upon water addition, were investigated as a function of increasing water concentration, mass fraction, in the interval 0.024-0.8. We measured: the complex permettivity in the frequency range 16Hz–50MHz; concentration dependence of both ϵ′ and ϵ′ at the different frequencies; the thermally stimulated dialectric polarization release (TSD); and the electro-optical behavior. The different structures that develop in isotropic microemulsions as water is added, were analyzed. An accurate description of the temperature-dependent relaxation processes occuring both in the isotropic state and in the LC phase of these systems was obtained and their activation energy and relaxation time calculated. Two different structures, of lyotropic nature, respectively of cylindrical and lamellar type, were identified; their concentration range of existence and temperature domain were determined. The concentration regions where the transition occurs from an isotropic microemulsion to an LC mesophase (0.3–0.48) and from the first to the second lyotropic LC structure (0.580-0.605) were also investigated.

Changed Lyotropic Liquid Crystalline Structure Due to Polymerization of the Amphiphilic Component

Optical patterns in polarized light and x-ray reflections in the low-angle region were used to detect a shift from one liquid crystalline structure to another during polymerization. The polymerization took place in a Iotropic liquid crystal of water and sodium undecenoate, with a structure consisting of cylinders in a two-dimensional hexagonal close packing. After polymerization, a lamellar liquid crystalline structure was obtained.