Eutectic Resolves Lysolipid Paradox in Thermoresponsive Liposomes.

A better molecular understanding of the temperature-triggered drug release from lysolipid-based thermosensitive liposomes (LTSLs) is needed to overcome the recent setbacks in developing this important drug delivery system. Enhanced drug release was previously rationalized in terms of detergent-like effects of the lysolipid monostearyl lysophosphatidylcholine (MSPC), stabilizing local membrane defects upon LTSL lipid melting. This is highly surprising and here referred to as the 'lysolipid paradox,' because detergents usually induce the opposite effect─they cause leakage upon freezing, not melting. Here, we aim at better answers to (i) why lysolipid does not compromise drug retention upon storage of LTSLs in the gel phase, (ii) how lysolipids can enhance drug release from LTSLs upon lipid melting, and (iii) why LTSLs typically anneal after some time so that not all drug gets released. To this end, we studied the phase transitions of mixtures of dipalmitoylphosphatidylcholine (DPPC) and MSPC by a combination of differential scanning and pressure perturbation calorimetry and identified the phase structures with small- and wide-angle X-ray scattering (SAXS and WAXS). The key result is that LTSLs, which contain the standard amount of 10 mol % MSPC, are at a eutectic point when they release their cargo upon melting at about 41 °C. The eutectic present below 41 °C consists of a MSPC-depleted gel phase as well as small domains of a hydrocarbon chain interdigitated gel phase containing some 30 mol % MSPC. In these interdigitated domains, the lysolipid is stored safely without compromising membrane integrity. At the eutectic temperature, both the MSPC-depleted bilayer and interdigitated MSPC-rich domains melt at once to fluid bilayers, respectively. Intact, fluid membranes tolerate much less MSPC than interdigitated domains─where the latter have melted, the high local MSPC content causes transient pores. These pores allow for fast drug release. However, these pores disappear, and the membrane seals again as the MSPC distributes more evenly over the membrane so that its local concentration decreases below the pore-stabilizing threshold. We provide a pseudobinary phase diagram of the DPPC-MSPC system and structural and volumetric data for the interdigitated phase.

Amorphous Aluminosilicate Nanosheets as Universal Precursors for the Synthesis of Diverse Zeolite Nanosheets for Polymer-Cracking Reactions.

Zeolites catalyze some reactions in their molecular-sized pores, but large molecules can react only on their external surface. Zeolite-nanosheets (NSs) have been developed as catalysts for large molecules. The previously reported methods to synthesize zeolite-NSs are specialized for each zeolite type. Here we propose a new method to synthesize various zeolite-NSs from the same amorphous aluminosilicate NSs (AAS-NSs) as a universal precursor. We successfully synthesized the unprecedented AAS-NSs in the hydrophilic space of the stable hyperswollen lyotropic lamellar (HL) phase. The four zeolite types could be obtained from the single-species AAS-NSs. These results imply that this method enables us to synthesize almost all types of zeolite-NSs. Moreover, the synthesized CHA-NSs have great potential for various applications because of their thickness and large external surface area.

Inclusion of Laponite nanoparticles in a lyotropic lamellar phase.

In this work, we consider a ternary system formed by a surfactant with a lamellar phase (lecithin) that was doped with a solution of Laponite at 1% by volume. The inclusion of nanoparticles in the lamellar phase was investigated by the small-angle X-ray scattering (SAXS) technique, which revealed three types of structures according to the observed scattering pattern. The lamellar period increased linearly with hydration up to a certain limit; this type of behavior is not the same as that found for a similar system using AOT as a surfactant. In the region that corresponds to an isotropic phase, it was observed that the period corresponds to 60 Å, and in the lamellar system of pure lecithin, with the same volumetric fraction (1/φ = 0.66), the corresponding periodicity is 62 Å, indicating that the presence of Laponite nanoparticles increases the attractive interaction, reducing the lamellar period, causing the bilayer to become more rigid, that is, with less fluctuations. In the more diluted region, the periodicity reached a limit value of 64 Å, which is slightly higher than the lamellar system in the absence of Laponite particles, so there was an expansion of the lamellar phase due to the lack of consistency of Laponite nanoparticles. In the more concentrated lamellar phase (under strong confinement), it was observed that the distance between the bilayers decreased, establishing a long-range order.

An image-processing method to detect sub-optical features based on understanding noise in intensity measurements.

Accurate quantitative analysis of image data requires that we distinguish between fluorescence intensity (true signal) and the noise inherent to its measurements to the extent possible. We image multilamellar membrane tubes and beads that grow from defects in the fluid lamellar phase of the lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine dissolved in water and water-glycerol mixtures by using fluorescence confocal polarizing microscope. We quantify image noise and determine the noise statistics. Understanding the nature of image noise also helps in optimizing image processing to detect sub-optical features, which would otherwise remain hidden. We use an image-processing technique "optimum smoothening" to improve the signal-to-noise ratio of features of interest without smearing their structural details. A high SNR renders desired positional accuracy with which it is possible to resolve features of interest with width below optical resolution. Using optimum smoothening, the smallest and the largest core diameter detected is of width [Formula: see text] and [Formula: see text] nm, respectively, discussed in this paper. The image-processing and analysis techniques and the noise modeling discussed in this paper can be used for detailed morphological analysis of features down to sub-optical length scales that are obtained by any kind of fluorescence intensity imaging in the raster mode.

Contribution of galactoglycerolipids to the 3-dimensional architecture of thylakoids.

Thylakoid membranes, the universal structure where photosynthesis takes place in all oxygenic photosynthetic organisms from cyanobacteria to higher plants, have a unique lipid composition. They contain a high fraction of 2 uncharged glycolipids, the galactoglycerolipids mono- and digalactosyldiacylglycerol (MGDG and DGDG, respectively), and an anionic sulfolipid, sulfoquinovosediacylglycerol (SQDG). A remarkable feature of the evolution from cyanobacteria to higher plants is the conservation of MGDG, DGDG, SQDG, and phosphatidylglycerol (PG), the major phospholipid of thylakoids. Using neutron diffraction on reconstituted thylakoid lipid extracts, we observed that the thylakoid lipid mixture self-organizes as a regular stack of bilayers. This natural lipid mixture was shown to switch from hexagonal II toward lamellar phase on hydration. This transition and the observed phase coexistence are modulated by the fine-tuning of the lipid profile, in particular the MGDG/DGDG ratio, and by the hydration. Our analysis highlights the critical role of DGDG as a contributing component to the membrane stacking via hydrogen bonds between polar heads of adjacent bilayers. DGDG interactions balance the repulsive electrostatic contribution of the charged lipids PG and SQDG and allow the persistence of regularly stacked membranes at high hydration. In developmental contexts or in response to environmental variations, these properties can contribute to the highly dynamic flexibility of plastid structure.

Phase Coexistence in a Dynamic Phase Diagram.

Metastability and phase coexistence are important concepts in colloidal science. Typically, the phase diagram of colloidal systems is considered at the equilibrium without the presence of an external field. However, several studies have reported phase transition under mechanical deformation. The reason behind phase coexistence under shear flow is not fully understood. Here, multilamellar vesicle (MLV)-to-sponge (L3 ) and MLV-to-Lα transitions upon increasing temperature are detected using flow small-angle neutron scattering techniques. Coexistence of Lα and MLV phases at 40 °C under shear flow is detected by using flow NMR spectroscopy. The unusual rheological behavior observed by studying the lamellar phase of a non-ionic surfactant is explained using (2) H NMR and diffusion flow NMR spectroscopy with the coexistence of planar lamellar-multilamellar vesicles. Moreover, a dynamic phase diagram over a wide range of temperatures is proposed.

Lamellar Lα mesophases doped with inorganic nanoparticles.

The development of nanostructured hybrid systems is a flourishing area of research, which brings together chemistry, physics and materials science. These systems are composed of nanoparticles with interesting properties (e.g. optical, magnetic, catalytic) dispersed within an organic matrix. Control of both the position and orientation of the particles in a precise and reproducible way is an important goal. Towards this goal, the use of lyotropic liquid crystals as host phases is a promising strategy that has prompted sustained experimental work over the last decade. Here we briefly review this field, with an emphasis on the structure and the physical characterization of these novel materials.

Urea as hydrogelator of surfactants.

HYPOTHESIS: The formation of adducts via urea interaction with distinct classes of surfactants (cationic, anionic, nonionic, and zwitterionic), leading to their assembly into lamellar structures and subsequent formation of hydrogels. The characteristics of these hydrogels are associated with both, the length of the alkyl chain, and the specific head group of the surfactant molecules. EXPERIMENTS: Characterization of adduct formation was conducted using Wide-Angle X-ray Scattering (WAXS), while Small-Angle X-ray Scattering (SAXS) was employed to probe the subsequent assembly into lamellar structures. The kinetics of hydrogel formation were assessed through rheological measurements and observed thermal transitions utilizing Differential Scanning Calorimetry (DSC). FINDINGS: The investigation revealed a universal propensity for hydrogel formation across all surfactant classes. The formation arises from the interactions between urea molecules via hydrogen bonding, forming adducts around the surfactant chains. In sequence, the adducts self-assemble in lamellae. This process constructs the intricate three-dimensional network characteristic of the hydrogel. Furthermore, the kinetics of hydrogel formation, and their rheological properties under equilibrated conditions, were found to be significantly influenced by the nature of the polar head group of the surfactant molecules. This is the first evidence on the formation of adducts of urea with classes of surfactants. As they are common components in cosmetic, supramolecular hydrogels have high potential to be used in formulations.

DEVELOPMENT AND EVALUATION OF NANOSTRUCTURED SYSTEMS FOR CUTANEOUS DELIVERY OF H2S-RELEASING CORTICOSTEROIDS FOR SKIN INFLAMMATORY DISEASES.

Psoriasis is an immune-mediated chronic inflammatory disease that causes major psychosocial impact. Topical corticosteroids represent the standard pharmacological treatment for mild-to-moderate disease, but their local and systemic adverse effects reinforce the need for treatment innovations. Here we developed lamellar phase-based formulations for topical delivery of a hybrid dexamethasone and hydrogen sulfide (H2S) donor molecule (Dexa-TBZ), aiming to potentiate the effects of the glucocorticoid with H2S. They offer the possibility to obtain precursor formulations free of water that originate lamellar phases upon water addition, preventing drug hydrolysis during storage. Two groups of formulations were developed varying the surfactants and oil phase types and content. Systems containing 20 and 70% of water formed, respectively, bulk lamellar phase and a more fluid formulation consisting of dispersed droplets (< 1000 nm) stabilized by lamellar phase. Both presented pseudoplastic behavior. Dexa-TBZ was incorporated at 1%, remaining stable for 8 h. Drug content decreased to ∼80% after 1 week in precursor formulations free of water, but remained stable after that. Without causing changes to the cutaneous barrier function ex vivo or to the histological structure of the skin in vivo, the formulation containing phosphatidylcholine as surfactant and 70% of water promoted 1.8- and 2.7-fold increases in Dexa-TBZ penetration in the stratum corneum and epidermis+dermis, respectively, compared to a control solution, demonstrating their potential applicability as topical delivery systems.

Thermotropic and lyotropic behaviour of new liquid-crystalline materials with different hydrophilic groups: synthesis and mesomorphic properties.

Several new calamitic liquid-crystalline (LC) materials with flexible hydrophilic chains, namely either hydroxy groups or ethylene glycol units, or both types together, have been synthesized in order to look for new functional LC materials exhibiting both, thermotropic and lyotropic behaviour. Such materials are of high potential interest for challenging issues such as the self-organization of carbon nanotubes or various nanoparticles. Thermotropic mesomorphic properties have been studied by using polarizing optical microscopy, differential scanning calorimetry and X-ray scattering. Four of these nonchiral and chiral materials exhibit nematic and chiral nematic phases, respectively. For some molecular structures, smectic phases have also been detected. A contact sample of one of the prepared compounds with diethylene glycol clearly shows the lyotropic behaviour; namely a lamellar phase was observed. The relationship between the molecular structure and mesomorphic properties of these new LCs with hydrophilic chains is discussed.

Ferrihydrite nanoparticles entrapped in shear-induced multilamellar vesicles.

HYPOTHESIS: Ferrihydrite (Fh) nanoparticles are receiving considerable scientific interest due to their large reactive surface areas, crystalline structures, and nanoparticle morphology. They are of great importance in biogeochemical processes and have the ability to sequester hazardous and toxic substances. Here, the working hypothesis was to entrap fractal-like Fh nanoparticles, with a radius of gyration of 6.2 nm and a primary building block of polydisperse spheres with a radius of 0.8 nm, in a shear-induced multilamellar vesicle (MLV) state using a 40 wt% polyethylene glycol dodecyl ether surfactant. EXPERIMENTS: Small- and Wide- Angle X-ray scattering revealed the equilibrium state of the non-ionic planar lamellar phase, the Fh dispersion, and their mixture. The MLV state was induced by using a shear flow in a Taylor-Couette geometry of a rheometer. FINDINGS: The nonionic surfactant initially exhibited a lamellar gel phase with two distinct d-spacings of 11.0 and 9.7 nm, which collapsed into the MLV state under shear flow. The Fh nanoparticles induced bilayer attraction by suppressing lamellar layer undulations, decreasing the d-spacing. These results are helpful in the understanding of the relationship between nanoparticle size and nanoparticle-bilayers interactions and provides insight on Fh encapsulations in a kinetically stable MLVs state.

Bending elastic modulus of a polymer-doped lyotropic lamellar phase.

The effect of inserting a neutral water-soluble adsorbing polymer on the flexibility of amphiphilic bilayers in a lamellar phase is investigated. The Lα system is a stack of charged undulating bilayers composed of sodium dodecyl sulfate (SDS) and octanol separated by aqueous solutions of polyethylene glycol (PEG). The mean bending elastic modulus κ is determined from the quadrupole splittings in the solid state NMR spectra of the perdeuterated octanol chains embedded in the membranes that undergo collective fluctuations. Parameters for describing the membrane behavior (bilayer thickness, elastic compressibility modulus, order parameter) are obtained by supplementing the NMR data with complementary experiments (x-ray scattering), NMR spectral simulations, and theoretical considerations. A fairly complete picture of the membrane rigidity emerges for any location in the lamellar phase thanks to a broad sweep of the lamellar domain by systematically varying the membrane fraction along dilution lines as well as the polymer composition. The most remarkable result is the difference between dilute and semi-dilute regimes. In the dilute PEG solution, no (or slight positive shift) polymer contribution to the rigidity curvature of the layered system is noted within the experimental resolution (≤0.3 kBT) and κ remains around 2.7 kBT. In contrast, the membrane rigidity increases steadily upon polymer addition once the crossover concentration cp* is exceeded, amounting to a 60% increase in κ at polymer concentration 2.5 cp* in the aqueous interlayers. These results are discussed with regard to the theoretical expectation of membrane rigidification upon irreversible polymer adsorption.

Preclinical study of methotrexate-based hydrogels versus surfactant based liquid crystal systems on psoriasis treatment.

Psoriasis is an autoimmune, inflammatory and chronic skin disease in which cell growth and proliferation are increased, causing erythema, lesions and skin's peeling. Oral methotrexate (MTX) is the first-choice drug when phototherapy or retinoid treatment are not effective. Topical administration can be advantageous to better orientate the drug's delivery; however, the stratum corneum performs as a barrier for hydrofilic drugs penetration. This study sought to evaluate two different types of vehicles for MTX on the psoriasis treatment - hydrogel and liquid crystal systems (LCs). Lamellar and hexagonal liquid crystalline phases were selected from a ternary phase diagram based on polysorbate 80, isopropyl miristate and water. The hydrogel was based on alkylated carbomer (ACH). Rheological analysis showed ACH was more elastic than lamellar and hexagonal phases. ACH interacted better with pig skin than LCs in bioadhesion assay. Preclinical study revealed the ACH decreased inflammation in mice with induced psoriasis, being as effective as dexamethasone to regulate epidermis thickness, COX-2 and myeloperoxidase activity and TNF-α level, while LCs demonstrated inflammatory effect. Therefore, MTX-loaded hydrogel based platforms are indicated for local treatment of psoriasis and present great potential for further studies.

Glycolipid Biosurfactants, Mannosylerythritol Lipids: Distinctive Interfacial Properties and Applications in Cosmetic and Personal Care Products.

Biosurfactants produced by a variety of microorganisms show attractive properties (e.g., higher surface activity and biodegradability, lower toxicity, and environmental compatibility) compared to chemically synthesized counterparts. The numerous advantages of biosurfactants have prompted their application to not only the food, cosmetic, and pharmaceutical industries, but agriculture and environmental protection disciplines as well. Among different types of biosurfactants, glycolipids are the most practically useful, due to their high product titers from renewable resources and versatile interfacial and biochemical properties. Mannosylerythritol lipids (MELs) are characteristic glycolipid biosurfactants that are produced by different yeast strains of the genus Pseudozyma. MELs exhibit different lyotropic liquid crystalline phases, such as sponge (L3), reverse bicontinuous cubic (V2), or lamellar (Lα) phases; and they have high levels of surface activity at very low concentrations. MELs also show excellent moisturizing effects on human skin and hair, with comparable performance to natural ceramides. Today, MELs are commercially produced by a Japanese company and their use is rapidly expanding around the world. In this review, we will briefly describe the current R&D status of glycolipid biosurfactants, with a focus on the interfacial properties of MELs and their applications in cosmetic and personal care products.

Effect of deuteration on the phase behaviour and structure of lamellar phases of phosphatidylcholines - Deuterated lipids as proxies for the physical properties of native bilayers.

Deuteration of phospholipids is a common practice to elucidate membrane structure, dynamics and function, by providing selective visualisation in neutron scattering, nuclear magnetic resonance and vibrational spectroscopy. It is generally assumed that the properties of the deuterated lipids are identical to those of the protiated lipids, and while a number of papers have compared the properties of different forms, to date this has been no systematic study of the effects over a range of conditions. Here we present a study of the effects of deuteration on the organisation and phase behaviour of four common phospholipids (DSPC, DPPC, DMPC, DOPC), observing the effect of chain deuteration and headgroup deuteration on lipid structure and phase behaviour. For saturated lipids in excess water the gel-fluid phase transition temperature is 4.3 ± 0.1 °C lower for lipids with deuterated chains compared to protiated chains, consistent with previous work. Despite this significant change, well away from the transition structural changes as measured by powder small angle X-ray scattering are small and within errors. To investigate this further, measurements were carried out on oriented multilamellar stacks of DOPC in the fluid phase at reduced hydration. Neutrons are used in conjunction with contrast variation to elucidate the role of the deuteration explicitly. It is found that deuterated chains cause a reduction in the lamellar repeat spacing and bilayer thickness, but deuterated headgroups cause an increase. Consequences for the interpretation of Neutron Scattering data with deuterated lipids are discussed.

Improvement of cutaneous delivery of methylene blue by liquid crystals.

The purpose of this study was to evaluate the effect of composition and characteristics of liquid crystalline phases (LCPs) on cutaneous delivery of methylene blue (MB). LCPs were obtained by mixing Brij97® with water at various ratios; Brij97®:water at 8:2 (F8:2), 7:3 (F7:3), and 6:4 (F6:4) were selected, and MB was incorporated at 0.1%. F8:2 and F7:3 exhibited textures and small angle X-ray scattering (SAXS) patterns corresponding to lamellar phase, whereas F6:4 displayed characteristics of hexagonal phase. All three LCPs were stable for 9 months, and exhibited thixotropic pseudoplastic behaviour. Increasing water content increased viscosity. All three LCPs released less (3.2- to 6.6-fold) MB than control gel (3.0% hydroxyethylcellulose (HEC) + 0.1% MB), demonstrating their ability to sustain release. Despite the lower release, all LCPs improved skin retention of MB at 6 h post-application (1.3- to 2.1-fold) compared to the control gel. Among the LCPs, F8:2-mediated skin retention of MB was more pronounced, followed by F7:3. Consistent with the increased penetration, transepidermal water loss (TEWL) also increased after treatment with the LCPs (2.0-2.8 fold), which suggests their influence on skin barrier. Irritation studies by Hen's Egg Test - Chorioallantoic Membrane (HET-CAM) suggest that F7:3 and F6:4 may be better tolerated by the skin than F8:2.

Reversible Control of Spacing in Charged Lamellar Membrane Hydrogels by Hydrophobically Mediated Tethering with Symmetric and Asymmetric Double-End-Anchored Poly(ethylene glycol)s.

Complex materials often achieve their remarkable functional properties by hierarchical assembly of building blocks via competing and/or synergistic interactions. Here, we describe the properties of new double-end-anchored poly(ethylene glycol)s (DEA-PEGs)-macromolecules designed to impart hydrophobically mediated tethering attractions between charged lipid membranes. We synthesized DEA-PEGs (MW 2000 (2K) and 4.6K) with two double-tail (symmetric) or a double-tail and a single-tail (asymmetric) hydrophobic end anchors and characterized their equilibrium and kinetic properties using small-angle X-ray scattering. Control multilayer membranes without and with PEG lipid (i.e., single-end-anchored PEG) swelled continuously, with the interlayer spacing increasing between 30 and 90 wt % water content due to electrostatic as well as, in the case of PEG lipid, steric repulsion. In contrast, interlayer spacings in lamellar membrane hydrogels containing DEA-PEGs expanded over a limited water dilution range and reached a "locked" state, which displayed a near constant membrane wall-to-wall spacing (δw) with further increases in water content. Remarkably, the locked state displays a simple relation to the PEG radius of gyration δw ≈ 1.6 RG for both 2K and 4.6K PEG. Nevertheless, δw being considerably less than the physical size of PEG (2(5/3)1/2 RG) is highly unexpected and implies that, compared to free PEG, anchoring of the PEG tether at both ends leads to a considerable distortion of the PEG conformation confined between layers. Significantly, the lamellar hydrogel may be designed to reversibly transition from a locked to an unlocked (membrane unbinding) state by variations in the DEA-PEG concentration, controlling the strength of the interlayer attractions due to bridging conformations. The findings with DEA-PEGs have broad implications for hydrophobic-mediated assembly of lipid- or surfactant-coated building blocks with distinct shape and size, at predictable spacing, in aqueous environments.

Exploring the in meso crystallization mechanism by characterizing the lipid mesophase microenvironment during the growth of single transmembrane α-helical peptide crystals.

The proposed mechanism for in meso crystallization of transmembrane proteins suggests that a protein or peptide is initially uniformly dispersed in the lipid self-assembly cubic phase but that crystals grow from a local lamellar phase, which acts as a conduit between the crystal and the bulk cubic phase. However, there is very limited experimental evidence for this theory. We have developed protocols to investigate the lipid mesophase microenvironment during crystal growth using standard procedures readily available in crystallography laboratories. This technique was used to characterize the microenvironment during crystal growth of the DAP12-TM peptide using synchrotron small angle X-ray scattering (SAXS) with a micro-sized X-ray beam. Crystal growth was found to occur from the gyroid cubic mesophase. For one in four crystals, a highly oriented local lamellar phase was observed, providing supporting evidence for the proposed mechanism for in meso crystallization. A new observation of this study was that we can differentiate diffraction peaks from crystals grown in meso, from peaks originating from the surrounding lipid matrix, potentially opening up the possibility of high-throughput SAXS analysis of in meso grown crystals.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'.

Antimicrobial Activity from Colistin-Heparin Lamellar-Phase Complexes for the Coating of Biomedical Devices.

Infections arising in hospitalized patients, particularly those who have undergone surgery and are reliant on receiving treatment through biomedical devices, continue to be a rising concern. It is well-known that aqueous mixtures of oppositely charged surfactant and polymer molecules can self-assemble to form liquid crystalline structures, primarily via electrostatically driven interactions that have demonstrated great potential as tailored-release nanomaterials. Colistin is a re-emerging antibiotic used against multidrug-resistant Gram-negative bacteria. Its amphiphilic structure allows it to form micellar aggregates in solution. Thus, the aim of this study was to determine whether structured complexes form between colistin and negatively charged biopolymers, such as the highly sulfated anticoagulant, heparin. Cross-polarized light microscopy and synchrotron small-angle X-ray scattering were employed to visualize the appearance of birefringent structures and identify liquid crystalline structures, respectively, formed across the interface between solutions of colistin and heparin. A lamellar phase with a lattice parameter of ∼40 Šwas formed upon contact between the oppositely charged solutions of colistin and heparin. In addition, in vitro release studies showed a slow release of colistin from the lamellar-phase gel complexes into the bulk media, and disk diffusion bioassays revealed antimicrobial activity against Pseudomonas aeruginosa. This system provides a novel, cost-effective, and simple approach to reducing the risk of infections by potentially applying the formulation as a coating for biomedical implants or tubing.

DOPC-DOPE composition dependent Lα-HII thermotropic phase transition: SAXD study.

The structural polymorphism and parameters of lyotropic phases formed in the mixed dioleoylphosphatidylcholine-dioleoylphosphatidylethanolamine (DOPC-DOPE) system upon heating and varying DOPC:DOPE composition were studied by means of small-angle X-ray diffraction (SAXD). In the temperature range 5-80°C a sequence of fluid lamellar Lα - inverse hexagonal HII - inverse cubic QII phases was detected at DOPE mole fractions XDOPE≥0.65. A superposition of two bicontinuous cubic QII phases of Pn3m and Ia3d space groups was identified. The Lα to HII phase transition temperature, the onset of the QII phase formation, as well as the lattice spacings of the Lα and HII phases were found to decrease with rising DOPE content. Moreover, evidence of structural rearrangement during the Lα to HII phase transition is given and change of transition mechanism with varying XDOPE is suggested.