Nonlamellar Liquid Crystalline Research Articles

PH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro Therapeutic Performance.

Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy.

PEGylation of Phosphatidylglycerol/Docosahexaenoic Acid Hexosomes with d-α-Tocopheryl Succinate Poly(ethylene glycol)2000 Induces Morphological Transformation into Vesicles with Prolonged Circulation Times.

Considering the broad therapeutic potential of omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA), here we study the effect of PEGylation of DHA-incorporated hexosomes on their physicochemical characteristics and biodistribution following intravenous injection into mice. Hexosomes were formed from phosphatidylglycerol and DHA with a weight ratio of 3:2. PEGylation was achieved through the incorporation of either d-α-tocopheryl succinate poly(ethylene glycol)2000 (TPGS-mPEG2000) or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol)2000 (DSPE-mPEG2000) at a concentration of 1.5 wt %. Nanoparticle tracking analysis, synchrotron small-angle scattering, and cryo-transmission electron microscopy were employed to characterize the nanodispersions. The results show that PEGylated lipids induce a structural transition from an inverse hexagonal (H2) phase inside the nanoparticles (hexosomes) to a lamellar (Lα) phase (vesicles). We also followed the effect of mouse plasma on the nanodispersion size distribution, number, and morphology because changes brought by plasma constituents could regulate the in vivo performance of intravenously injected nanodispersions. For comparative biodistribution studies, fluorescently labeled nanodispersions of equivalent quantum yields were injected intravenously into healthy mice. TPGS-mPEG2000-induced vesicles were most effective in avoiding hepatosplenic clearance at early time points. In an orthotopic xenograft murine model of glioblastoma, TPGS-mPEG2000-induced vesicles also showed improved localization to the brain compared with native hexosomes. We discuss these observations and their implications for the future design of injectable lyotropic nonlamellar liquid crystalline drug delivery nanosystems for therapeutic interventions of brain and liver diseases.

Structural investigation and steric stabilisation of Guerbet glycolipid-based cubosomes and hexosomes using triblock polyethylene oxide-polypropylene oxide-polyethylene oxide copolymers

Aqueous dispersions of inverse nonlamellar liquid crystalline nanostructures namely cubosomes and hexosomes have been used as carriers for drug delivery. The large surface area and internal water channel networks in these nanocarriers make them useful to transport amphiphilic, hydrophilic and hydrophobic active ingredients. However, suitable stabilisers that can maintain the colloidal stability and preserving the internal structures of the complex cubosomes and hexosomes are integral. Herein, Guerbet glycolipids namely 2-hexyl-decyl-β-D-glucopyranoside (β-Glc-OC10C6) and 2-hexyl-decyl-β-D-xylopyranoside (β-Xyl-OC10C6) were investigated for their potential in forming cubosomes and hexosomes respectively using Pluronic copolymers as steric stabilisers. The performance of five different Pluronics was evaluated for stabilisation of the dispersions, with a view to establish a structure-property relationship between the lipids and the stabilisers. The dispersions were assessed through synchrotron small-angle X-ray scattering as a function of temperature and the concentration of stabilisers. The internal structure of dispersed particles of β-Glc-OC10C6 was susceptible to changes upon stabilisation by different Pluronics and with increasing temperature. The lowest molecular weight Pluronic studied, L64, had the greatest propensity to disrupt the structure, suggesting that it is able to penetrate the internal structure to a greater degree than the other Pluronic stabilisers. In contrast, the β-Xyl-OC10C6 counterpart formed a stable inverse hexagonal phase structure that was invariant with the Pluronic used or temperature. The stability of the structure of β-Xyl-OC10C6 suggests it has greater potential for use in drug delivery applications and the studies overall extend the current understanding around the structures formed upon dispersion of Guerbet lipids.

Cell medium-dependent dynamic modulation of size and structural transformations of binary phospholipid/ω-3 fatty acid liquid crystalline nano-self-assemblies: Implications in interpretation of cell uptake studies

Lyotropic non-lamellar liquid crystalline (LLC) nanoparticles, with their tunable structural features and capability of loading a wide range of drugs and reporter probes, are emerging as versatile injectable nanopharmaceuticals. Secondary emulsifiers, such as Pluronic block copolymers, are commonly used for colloidal stabilization of LLC nanoparticles, but their inclusion often compromises the biological safety (e.g., poor hemocompatibility and enhanced cytotoxicity) of the formulation. Here, we introduce a library of colloidally stable, structurally tunable, and pH-responsive lamellar and non-lamellar liquid crystalline nanoparticles from binary mixtures of a phospholipid (phosphatidylglycerol) and three types of omega-3 fatty acids (ω-3 PUFAs), prepared in the absence of a secondary emulsifier and organic solvents. We study formulation size distribution, morphological heterogeneity, and the arrangement of their internal self-assembled architectures by nanoparticle tracking analysis, synchrotron small-angle X-ray scattering, and cryo-transmission electron microscopy. The results show the influence of type and concentration of ω-3 PUFAs in nanoparticle structural transitions spanning from a lamellar (Lα) phase to inverse discontinuous (micellar) cubic Fd3m and hexagonal phase (H2) phases, respectively. We further report on cell-culture medium-dependent dynamic fluctuations in nanoparticle size, number and morphology, and simultaneously monitor uptake kinetics in two human cell lines. We discuss the role of these multiparametric biophysical transformations on nanoparticle-cell interaction kinetics and internalization mechanisms. Collectively, our findings contribute to the understanding of fundamental steps that are imperative for improved engineering of LLC nanoparticles with necessary attributes for pharmaceutical development.

Temperature triggering of kinetically trapped self-assemblies in citrem-phospholipid nanoparticles

Lyotropic non-lamellar liquid crystalline (LLC) nanoparticles are attractive nanocarriers for drug delivery, particularly for the solubilization of poorly water-soluble drugs. Due to the reported problems of complement activation and cytotoxicity of most investigated Pluronic F127-stabilized cubosomes and hexosomes, there is an interest in introducing safe stabilizers for these LLC nanodispersions. Citrem appears to be the stabilizer of choice for the colloidal stabilization of these LLC nano-self-assemblies owing to its hemocompatiblity and poor activation of the complement system. This anionic food-grade emulsifier in combination with soy phosphatidylcholine (SPC) can be used to introduce a library of hemocompatible lamellar and non-lamellar liquid crystalline nanodispersions at different lipid compositions. We found that batch-to-batch variability in citrem composition is associated with slight alterations in the size, structural characteristics, and surface charge of the produced citrem/SPC nanoparticles. Further, we report on the temperature-triggered alterations in these nano-self-assemblies at different lipid compositions by using synchrotron small angle X-ray scattering (SAXS). The addition of citrem at different temperatures induces lamellar to non-lamellar structural transitions as evident from the appearance of inverse bicontinuous cubic Pn3m and discontinuous hexagonal (H2) phases, respectively, upon increasing citrem concentration and varying temperature in the range of 5–59 °C. Citrem/SPC nanoparticles are attractive for use in the development of nanocarriers for drug delivery owing to their structural tunability and hemocompatiblity.

Nonlamellar liquid crystals: a new paradigm for the delivery of small molecules and bio-macromolecules.

The aim of this article is to collate the recent developments in the field of drug delivery, medical therapeutics and diagnostics specifically involving the nonlamellar liquid crystalline (NLC) systems. This review highlights different NLC phases having cubic, hexagonal and sponge internal structures, and their application in the field of drug delivery, such as dose reduction, toxicity reduction and therapeutic efficacy enhancement either in the form of nanoparticles, colloidal dispersion or gels. In addition, application of NLC systems as vehicles for peptides, proteins and as atheranostic system in cancer and other disease conditions is also elaborated, which is a growing platform of interest. Overall, the present review gives us a complete outlook on applications of NLC systemsin the field of medicine.

Cisplatin Encapsulation Generates Morphologically Different Multicompartments in the Internal Nanostructures of Nonlamellar Liquid-Crystalline Self-Assemblies.

Cisplatin ( cis-diamminedichloroplatinum(II)) is among the most potent cytotoxic agents used in cancer chemotherapy. The encapsulation of cisplatin in lipid-based drug carriers has been challenging owing to its low solubility in both aqueous and lipid phases. Here, we investigated cisplatin encapsulation in nonlamellar liquid-crystalline (LC) nanodispersions formed from a ternary mixture of phytantriol (PHYT), vitamin E (Vit E), and an anionic phospholipid [either phosphatidylglycerol (DSPG) or phosphatidylserine (DPPS)]. We show an increase in cisplatin encapsulation efficiency (EE) in nanodispersions containing 1.5-4 wt % phospholipid. The EE was highest in DPPS-containing nanodispersions (53-98%) compared to DSPG-containing counterparts (25-40%) under similar experimental conditions. Through structural and morphological characterizations involving synchrotron small-angle X-ray scattering and cryogenic transmission electron microscopy, we further show that varying the phospholipid content of cisplatin-free nanodispersions triggers an internal phase transition from a neat hexagonal (H2) phase to a biphasic phase (internal H2 phase coexisting with the lamellar (Lα) phase). However, cisplatin encapsulation in both DPPS- and DSPG-containing nanodispersions generates the coexistence of morphologically different multicompartments in the internal nanostructures comprising vesicles as a core, enveloped by an inverted-type surface bicontinuous cubic Im3 m (primitive, QIIP) phase or H2 phase. We discuss the biophysical basis of these drug-induced morphological alterations and provide insights into the potential development of inverted-type LC nanodispersions for cisplatin delivery.

Aripiprazole-loaded in Soft Lipidic Non-Lamellar Liquid Crystalline Nanostructures

Event Abstract Back to Event Aripiprazole-loaded in Soft Lipidic Non-Lamellar Liquid Crystalline Nanostructures Intan Diana Mat Azmi1* and Lai Y. Khen1 1 Putra Malaysia University, Malaysia Background Non-lamellar liquid crystalline (LC) nanostructures have recently received attention in application in drug delivery systems, due to their unique well-defined and tunable internal nanostructures. The rich polymorphism of LC nanostructures are considered as a key factor in improving loading efficiency of different types of poorly soluble therapeutic agents. This project is focused on developing Aripiprazole-loaded non-lamellar LC nanostructures, consisted of a binary mixture of soy phosphatidylcholine (SPC) and citric acid ester of monoglyceride (citrem). Aripiprazole is a psychotropic drug that used to treat schizophrenia and bipolar disorder, which showed poor aqueous solubility of less than 0.3 μg/ ml. It is utmost interest to see the potential of non-lamellar LC nanoparticles in improving the loading efficiency of Aripiprazole by entrapping the drugs into their well-order internal nanostructures. Methods The investigated drug-free and drug-loaded nanodispersions were prepared based on a lipid ratio of SPC:Citrem (1:1 wt/wt) at 5 wt% lipid concentration via high energy ultrasonication. The characterizations were done to determine the particle size, stability, morphology, encapsulation efficiency and the interaction between the drugs and the nanodispersions. Results The results show that Aripiprazole, at three different concentrations (0.1, 0.2, and 0.25 wt%), were successfully loaded into LC nanoparticles where the encapsulation efficiency was all above 92%. The particle size of LC nanoparticles produced was in the range of 154.1-183.4nm, with polydispersity index, PDI 0.103-0.172, and zeta potential of -26.0mV to -29.1mV. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) showed that there was a chemical interaction between Aripiprazole and LC nanoparticles, while Transmission Electron Microscopy (TEM) was used to see the morphology and overall size distribution of drug-free and drug-loaded nanodispersions. Conclusion This study suggests the potential use of non-lamellar LC nanodispersions as a promising nanocarrier for Aripiprazole delivery, which is expected to improve the pharmacokinetics and stability of this drug. Acknowledgements Authors would like to thank Universiti Putra Malaysia for the IPM grant. Keywords: Liquid crystalline nanostructures, aripiprazole, Drug delivery, Schizophrenia, Nanoparticle (NP) Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Poster Presentation Topic: Mental health Citation: Mat Azmi I and Khen LY (2019). Aripiprazole-loaded in Soft Lipidic Non-Lamellar Liquid Crystalline Nanostructures. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00050 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Oct 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Intan Diana Mat Azmi, Putra Malaysia University, Seri Kembangan, Malaysia, intandiana@upm.edu.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Intan Diana Mat Azmi Lai Y Khen Google Intan Diana Mat Azmi Lai Y Khen Google Scholar Intan Diana Mat Azmi Lai Y Khen PubMed Intan Diana Mat Azmi Lai Y Khen Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Structural Investigation of Bulk and Dispersed Inverse Lyotropic Hexagonal Liquid Crystalline Phases of Eicosapentaenoic Acid Monoglyceride.

Recent studies demonstrated the potential therapeutic use of newly synthesized omega-3 (ω-3) polyunsaturated fatty acid (PUFA) monoglycerides owing to their beneficial health effects in various disorders including cancer and inflammation diseases. To date, the research was mainly focused on exploring the biological effects of these functional lipids. However, to the best of our knowledge, there is no report on the hydration-mediated self assembly of these lipids that leads to the formation of nanostructures, which are attractive for use as vehicles for the delivery of drugs and functional foods. In the present study, we investigated the temperature-composition phase behaviour of eicosapentaenoic acid monoglyceride (MAG-EPA), which is one of the most investigated ω-3 PUFA monoglycerides, during a heating-cooling cycle in the temperature range of 5-60 °C. Experimental synchrotron small-angle X-ray scattering (SAXS) evidence on the formation of a dominant inverse hexagonal (H2) lyotropic liquid crystalline phase and its temperature-induced transition to an inverse micellar solution (L2 phase) is presented for the fully hydrated bulk MAG-EPA system and its corresponding dispersion. We produced colloidal MAG-EPA hexosomes with an internal inverse hexagonal (H2) lyotropic crystalline phase in the presence of F127, a well-known polymeric stabilizer, or citrem, which is a negatively charged food-grade emulsifier. In this work, we report also on the formation of MAG-EPA hexosomes by vortexing MAG-EPA in excess aqueous medium containing F127 at room temperature. This low-energy emulsification method is different than most reported studies in the literature that have demonstrated the need for using a high-energy input during the emulsification step or adding an organic solvent for the formation of such colloidal nonlamellar liquid crystalline dispersions. The designed nanoparticles hold promise for future drug and functional food delivery applications due to their unique structural properties and the potential health-promoting effects of MAG-EPA.

Non-lamellar lipid assembly at interfaces: controlling layer structure by responsive nanogel particles.

Biological membranes do not only occur as planar bilayer structures, but depending on the lipid composition, can also curve into intriguing three-dimensional structures. In order to fully understand the biological implications as well as to reveal the full potential for applications, e.g. for drug delivery and other biomedical devices, of such structures, well-defined model systems are required. Here, we discuss the formation of lipid non-lamellar liquid crystalline (LC) surface layers spin-coated from the constituting lipids followed by hydration of the lipid layer. We demonstrate that hybrid lipid polymer films can be formed with different properties compared with the neat lipid LC layers. The nanostructure and morphologies of the lipid films formed reflect those in the bulk. Most notably, mixed lipid layers, which are composed of glycerol monooleate and diglycerol monooleate with poly(N-isopropylacrylamide) nanogels, can form films of reverse cubic phases that are capable of responding to temperature stimulus. Owing to the presence of the nanogel particles, changing the temperature not only regulates the hydration of the cubic phase lipid films, but also the lateral organization of the lipid domains within the lipid self-assembled film. This opens up the possibility for new nanostructured materials based on lipid-polymer responsive layers.

Citrem modulates internal nanostructure of glyceryl monooleate dispersions and bypasses complement activation: Towards development of safe tunable intravenous lipid nanocarriers

Lyotropic non-lamellar liquid crystalline (LLC) aqueous nanodispersions hold a great promise in drug solubilization and delivery, but these nanosystems often induce severe hemolysis and complement activation, which limit their applications for safe intravenous administration. Here, we engineer and characterize LLC aqueous nanodispersions from a binary lipid mixture consisting of 2,3-dihydroxypropyl oleate (glyceryl monooleate) and medium-chain triglycerides with tunable internal nanostructures and improved hemocompatibility controlled by citrem as stabilizer. Citrem, in a concentration-dependent manner, modulates the internal nanostructure of LLC dispersions from a biphasic H2/L2 feature to a neat L2 phase, where the latter resembles “thread-like” swollen micelles. Citrem stabilization totally overcomes hemolysis and complement activation, thus realizing the potential of the engineered LLC aqueous nanodispersions for exploitation in intravenous delivery of drugs and contrast agents. From the Clinical EditorThe complement system often gets activated after intravenous injection of nano drug-carriers. This may result in detrimental systemic effects. The authors described in this article the use of citrem as a stabilizing agent and showed the ability of this agent to abolish complement activation. Hence, citrem may prove to be an important component of tunable LLC nanocarriers that may be useful in future clinical setting.

PEGylation of phytantriol-based lyotropic liquid crystalline particles--the effect of lipid composition, PEG chain length, and temperature on the internal nanostructure.

Poly(ethylene glycol)-grafted 1,2-distearoyl-sn-glycero-3-phosphoethanolamines (DSPE-mPEGs) are a family of amphiphilic lipopolymers attractive in formulating injectable long-circulating nanoparticulate drug formulations. In addition to long circulating liposomes, there is an interest in developing injectable long-circulating drug nanocarriers based on cubosomes and hexosomes by shielding and coating the dispersed particles enveloping well-defined internal nonlamellar liquid crystalline nanostructures with hydrophilic PEG segments. The present study attempts to shed light on the possible PEGylation of these lipidic nonlamellar liquid crystalline particles by using DSPE-mPEGs with three different block lengths of the hydrophilic PEG segment. The effects of lipid composition, PEG chain length, and temperature on the morphology and internal nanostructure of these self-assembled lipidic aqueous dispersions based on phytantriol (PHYT) were investigated by means of synchrotron small-angle X-ray scattering and Transmission Electron Cryo-Microscopy. The results suggest that the used lipopolymers are incorporated into the water-PHYT interfacial area and induce a significant effect on the internal nanostructures of the dispersed submicrometer-sized particles. The hydrophilic domains of the internal liquid crystalline nanostructures of these aqueous dispersions are functionalized, i.e., the hydrophilic nanochannels of the internal cubic Pn3m and Im3m phases are significantly enlarged in the presence of relatively small amounts of the used DSPE-mPEGs. It is evident that the partial replacement of PHYT by these PEGylated lipids could be an attractive approach for the surface modification of cubosomal and hexosomal particles. These PEGylated nanocarriers are particularly attractive in designing injectable cubosomal and hexosomal nanocarriers for loading drugs and/or imaging probes.

Understanding the Interfacial Properties of Nanostructured Liquid Crystalline Materials for Surface-Specific Delivery Applications

Nonlamellar liquid crystalline dispersions such as cubosomes and hexosomes have great potential as novel surface-targeted active delivery systems. In this study, the influence of internal nanostructure, chemical composition, and the presence of Pluronic F127 as a stabilizer, on the surface and interfacial properties of different liquid crystalline particles and surfaces, was investigated. The interfacial properties of the bulk liquid crystalline systems with coexisting excess water were dependent on the internal liquid crystalline nanostructure. In particular, the surfaces of the inverse cubic systems were more hydrophilic than that of the inverse hexagonal phase. The interaction between F127 and the bulk liquid crystalline systems depended on the internal liquid crystalline structure and chemical composition. For example, F127 adsorbed to the surface of the bulk phytantriol cubic phase, while for monoolein cubic phase, F127 was integrated into the liquid crystalline structure. Last, the interfacial adsorption behavior of the dispersed liquid crystalline particles also depended on both the internal nanostructure and the chemical composition, despite the dispersions all being stabilized using F127. The findings highlight the need to understand the specific surface characteristics and the nature of the interaction with colloidal stabilizer for understanding and optimizing the behavior of nonlamellar liquid crystalline systems in surface delivery applications.

The Delivery of Lipidic Compounds to Model Membrane Interfaces by Non-lamellar Liquid Crystalline Nano-particles

There is an increasing demand for methods to study processes at the lipid-aqueous solution interface, due to the importance of lipids and lipid self-assembly structures as regulators both for biological activity and for drug delivery vehicles. The biological membrane is one of the most important interfaces that the drug delivery vehicles encounter. The potential use of non-lamellar lipid structures delivery systems in pharmaceutical, food and cosmetic applications has invoked a number of studies of the assembly and interactions of cubic phases of these materials. One such system is a colloidal dispersion of the cubic liquid crystalline phase of glycerol monooleate. We will discuss some aspects of what happens when these liquid crystalline lipid nanoparticle encounters a lipid bilayer, consisting dioleoylphosphaticylcholine, either as supported bilayer or as a vesicle. Null ellipsometry and QCM-D provides kinetic information about the adsorption and triggerable release of the nanoparticles. Using contrast matching of the supported lipid bilayer, neutron reflectivity makes it possible to assess the exchange of material from one ordered lipid phase to another. Synchrotron Small Angle X-Ray Diffraction allowed us to in detail study the phase transition when non-lamellar glycerol monooleate based nanoparticle interact with phospholipid vesicles. Together the four techniques provide insight into the interaction mechanism and shows that the release of the particles are likely to be caused by phase transition of the lipid self-assembled structures.

Nonlamellar Liquid Crystalline Phases and Their Particle Formation in the Egg Yolk Phosphatidylcholine/Diolein System

The phase behavior of fully hydrated egg yolk phosphatidylcholine (EPC)/diolein (DO) mixtures was investigated by small-angle X-ray scattering and 31P NMR. EPC formed a lamellar phase, whereas DO gave a negative curvature to the lipid membranes, leading to nonlamellar phase formation. At an EPC/DO molar ratio of 8:2, the mixture formed a bicontinuous cubic phase of primitive type. A bicontinuous cubic phase of diamond type was also observed at the ratio of 7:3, but it coexisted with an inverted hexagonal (HII) phase. The mixture with higher DO fractions formed the HII phase. We further investigated if these nonlamellar phases could be dispersed by high-pressure emulsification with Pluronic F127, to form cubosomes or hexosomes, as have been obtained in monoolein-based cubic and HII phases (Langmuir 2001, 17, 3917−3922; Langmuir 2002, 18, 9283−9288). As a result, cubosomes could not be obtained and vesicles were formed instead, presumably due to the existence of F127, which gave a positive curvature to the negatively curved membranes. However, the HII phase, which was less compatible with F127, could be dispersed to form hexosomes.