The addition of short-EO-chain polyoxyethylene dodecyl ether (C12EO n ) surfactants to a dilute solution of polyoxyethylene cholesteryl ether (ChEO m , m = 10 and 15) induced unidimensional micellar growth leading to the formation of viscoelastic solutions. The viscoelastic systems show Maxwellian behavior over a wide range of shear frequency and are considered to consist of a transient network of wormlike micelles. With increasing concentration of C12EO n (n = 1−4) at fixed ChEO10 concentration in a micellar solution phase, at first a gradual and then a steep increase in zero-shear viscosity (ηo) was observed. The mixing fraction of C12EO n to increase ηo or induce the micellar growth increases in the following order:  C12EO1 ≈ C12EO2 < C12EO3 < C12EO4. On increasing m of ChEO m from 10 to 15 in the ChEO m −C12EO3 system, a sharp increase in ηo is shifted to relatively higher mixing fraction of C12EO3. These results indicate that the average section area per surfactant in a micelle decreases upon the addition of short-EO-chain C12EO n and that micelles grow to form long rod micelles. Assuming that the cross-sectional area of each of the amphiphiles at the hydrophobic interface, a s, is constant (ideal surface mixing), the rod micellar length was calculated as a function of the mixing fraction of C12EO n in the total amphiphile, X, using the data obtained from experimental results. The calculated results on micellar growth well explained the results of rheological measurements.

No abstract

Gaining an increased understanding of the toxicity of new lipid nanoparticle formulations such as the class of cubic and hexagonal phase forming nanomaterials called cubosomes™ and hexosomes™ is crucial for their development as therapeutic agents. Surprisingly, the literature on the in vitro and in vivo toxicity of cubic and hexagonal phase forming lipid nanoparticles is negligible, despite a rapidly growing number of publications on their potential use in various therapeutic applications. In this work we have developed methods to study the in vitro cytotoxicity of two chemically distinct cubic phase nanoparticle dispersions using the lipids glycerol monooleate and phytantriol respectively. We have found that the toxicity of phytantriol cubosomes is considerably greater than that of glycerol monooleate cubosomes.The increased toxicity of phytantriol appears to result from its greater ability to disrupt the cellular membrane (haemolytic activity) and oxidative stress. This finding has significant impact and can provide useful guidelines for those conducting further research on the use of cubic phase forming lipids for therapeutic and diagnostic applications both in vitro and in vivo. † Electronic supplementary information (ESI) available. See

Different from conventional nonionic poly(oxyethylene) surfactants, poly(oxyethylene) cholesteryl ethers, ChEO n , possess a bulky and nonflexible hydrophobic part and form a variety of self-organized structures in water. We investigated the phase behavior and the micellar structures in the water/ChEO15 and water/ChEO10 systems by means of visual observation, rheometry, small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), dielectric relaxation spectroscopy (DRS), and densimetry. We found that in the water/ChEO15 system, aqueous micellar (Wm), discontinuous micellar cubic (I1) with Fd3m space group, hexagonal (H1), rectangular ribbon (R1), and lamellar (Lα) phases are formed, whereas Wm, unknown, R1, defected lamellar ( ), and Lα phases are produced in the water/ChEO10 system at ambient temperatures. Compared with a conventional aqueous nonionic surfactant system, the intermediate R1 phase region is incredibly wide. As for the water/ChEO15 system, with increasing water content, the packing parameter, P, in the R1 region is gradually decreased, finally converging to 1/2 at W s ∼ 0.58, indicative of the formation of the H1 phase. The R1 phase acts as a “distorted” hexagonal phase in the system. However, in the water/ChEO10 system, upon reduction of W S, P shows a steplike increase and the maximum value ∼0.67 at W S ∼ 0.7, just corresponding to the threshold of discontinuous and bicontinuous structures. After that, P is decreased with decreasing W S and unknown phase that cannot be indexed to any known space group for liquid crystalline phases emerges at W S ∼ 0.5. The GIFT analysis of the SAXS data for the Wm solution indicates that spherical micelles are present in the water/ChEO15 system in an ambient temperature range, but ChEO10 forms a short-rod micelle in water. With increasing temperature, rodlike micelles appear to be grown and a viscoelastic micellar phase is formed in water/ChEO10 system. The hydration number for each oxyethylene unit is evaluated as ∼4 by DRS, which gives a consistent explanation for the concentration dependence of the apparent hydrodynamic radius in the Wm phase obtained by DLS. Hydrated water molecules should be regarded as a constituent of the micelles. The majority of these features of novel phase behavior in the water/ChEO n systems are based on a nonflexible and bulky hydrophobic part of ChEO n .

A novel anionic gemini-type surfactant with no spacer group, disodium 2,3-didodecyl-1,2,3,4-butanetetracarboxylate (GS), was investigated for its phase behavior in water, water/decane, and water/cosurfactant systems in a wide range of compositions. At low surfactant concentration in the GS−water binary system, a micellar solution phase is formed which transforms to a hexagonal (H1) phase, as in conventional ionic surfactant systems. At high GS concentration, however, the H1 phase transforms to the rectangular-ribbon (R1) liquid−crystal phase. Since the GS molecule has no spacer group, a small cross-sectional area of the headgroup and closely packed hydrophobic chain tend to increase the packing constraints of the lipophilic core with increasing surfactant concentration, thereby inducing the H1−R1 phase transition. In the presence of a normal hydrocarbon like decane, the H1 phase is changed to a micellar cubic phase. On the other hand, the surfactant layer curvature becomes less positive upon addition of a lipophilic amphiphile because it is solubilized in the palisade layer of the aggregate. Addition of short poly(oxyethylene) chain nonionic surfactant (C m EO n , where m, n = 12, 3; 12, 4; and 16, 4) to the aqueous GS solution in a dilute region increases the viscosity by several orders and forms a transparent and viscoelastic micellar solution showing the rheological properties of typical wormlike micelles, with Maxwellian behavior in low oscillatory frequency. In the GS−C12EO3 and also in the GS−C16EO4 systems, the viscosity values are significantly higher than the reported values for dimeric surfactants of similar chain length.

Phase behavior of diglycerol fatty acid esters (Qn-D, where n represents the carbon number in the alkyl chain length of amphiphile, n = 10-16) were investigated in different nonpolar oils, liquid paraffin (LP70), squalane, and squalene. There is surfactant solid at lower temperature, and the surfactant solid does not swell in oil, and the melting temperature is almost constant in a wide range of compositions. In all of the systems, a lamellar liquid crystal (L(alpha)) is formed in a concentrated region at a temperature between the solid melting temperature and the isotropic two- or single-phase regions. In the dilute regions, reverse vesicles are formed in L(alpha) + O regions. There are two liquid-phase regions above the L(alpha) present region. This two-phase boundary corresponds to the cloud-point curve of nonionic surfactant aqueous solutions. However, instead of being less soluble in water at high temperature for the cloud point, the surfactant becomes more soluble in the organic solvents at high temperature. Namely, the effect of temperature on the solubility is opposite to the clouding phenomenon. When the hydrocarbon chain of the diglycerol surfactant decreases, the two-phase region becomes wider. In the case of a fixed surfactant, the surfactant is most miscible with squalene (narrowest two-phase regions) and the order of dissolutions tendency is squalene > LP70 > squalane. These results show that the hydrophilic moiety (diglycerol group) is more insoluble in oil compared with that of a conventional poly(oxyethylene)-type nonionic surfactant. Formation of reversed rodlike micelles was confirmed by SAXS scattering curve. When the hydrocarbon chain of surfactant is short, the micellar size becomes larger. In a fixed surfactant system, the reverse micellar size increases by changing oil from squalene to LP70. A small amount of water induces a dramatic elongation of reverse micelles.

No abstract

No abstract