Characterization of a complex dispersion of multilamellar vesicles

Spherulites ^® are multilamellar vesicles made up of surfactant bilayers. These vesicles would potentially be very useful for the encapsulation and protection of molecules; however, traditional formulations of these vesicles are poor at retaining small hydrophilic molecules (below 1000 g/mol). In this study, we present new systems of Spherulites called complex dispersions. These are prepared by dispersing Spherulites in an oil medium, and then emulsifying this oily dispersion of Spherulites within an aqueous solvent. These new systems provide an additional oil barrier between encapsulated molecules and an external aqueous phase. We have used polarized light optical microscopy, X-ray diffraction and freeze–fracture electron microscopy to study a complex dispersion of Spherulites at all stages of its preparation. We first studied the sheared lamellar phase, followed by the dispersion of the multilamellar vesicles in the oily medium and finally the emulsification of the oily dispersion within the aqueous solvent. We compared our results on lamellar phases with previous results obtained with Spherulites directly dispersible in an aqueous medium. Since the formulation of our lamellar phase included a large percentage of oil as a component, we studied the localization of the oil in the lamellar structure. We also studied the influence of osmotic pressure on complex dispersions, because complex dispersions possess a double structure similar to that of water-in-oil-in-water emulsions and multiple emulsions are known to be sensitive to osmotic pressure. In conclusion, complex dispersions proved to be new potential carriers exhibiting some unique physical properties.     

Weak surface energy in nematic dispersions: Saturn ring defects and quadrupolar interactions

The role of surface energy in the behavior of colloidal particles in liquid crystalline phases is investigated. When the surface energy dominates, a hedgehog defect is formed and, according to an electrostatic analogy, the distortions around the particles exhibit a dipolar character. By contrast, for weaker anchoring, the configuration becomes quadrupolar as evidenced by the structure of latex clusters in lyotropic systems and the observation of defects reminiscent of Saturn rings in thermotropic systems. Received 21 June 1999     

Selective complexation and transport of europium ions at the interface of vesicles

The aim of the present work was to design functionalized lipidic membranes that can selectively interact with lanthanide ions at the interface and to exploit the interaction between membranes induced by this molecular-recognition process with a view to building up self-assembled vesicles or controlling the permeability of the membrane to lanthanide ions. Amphiphilic molecules bearing a beta-diketone unit as head group were synthesized and incorporated into phospholipidic vesicles. Binding of Eu(III) ions to the amphiphilic ligand can lead to formation of a complex involving ligands of the same vesicle membrane (intravesicular complex) or of two different vesicles (intervesicular complex). The effect of Eu(III) ions on vesicle behavior was studied by complementary techniques such as fluorimetry, light scattering, and electron microscopy. The formation of an intravesicular luminescent Eu/beta-diketone ligand (1/2) complex was demonstrated. The linear increase in the binding constant with increasing concentration of ligands in the membrane revealed a cooperative effect of the ligands distributed in the vesicle membrane. The luminescence of this complex can be exploited to monitor the kinetics of complexation at the interface of the vesicles, as well as ion transport across the membrane. By encapsulation of 2,6-dipicolinic acid (DPA) as a competing ligand which forms a luminescent Eu/DPA complex, the kinetics of ion transport across the membrane could be followed. These functional vesicles were shown to be an efficient system for the selective transport of Eu(III) ions across a membrane with assistance by beta-diketone ligands.     

Inorganic Polymerization in a Non-Ionic Lyotropic Lamellar Phase

Silicon tetramethoxide was polymerized within a nonionic lyotropic lamellar phase. After gelation, the birefringence of the sample is preserved and polarized light optical microscope observations reveal no segregation. High Resolution Small Angle X-ray Scattering patterns of the gel shows Bragg peaks characteristic of a layered structure. Freeze fracture experiments on the lamellar gel show stacks of parallel bilayers. The experimental observations indicate that the silica is located in the lamellar structure.     

Effect of a neutral water-soluble polymer on the lamellar phase of a zwitterionic surfactant system

We have studied the effect of adding a water-soluble polymers (PEG) to the lamellar phases of the ternary system tetradecyldimethylaminoxide (C14DMAO)-hexanol-water. The results of Freeze-Fracture Electron Microscopy (FFEM) and Small Angle X-ray Scattering (SAXS) experiments show that the addition of the polymer induces the spontaneous formation of highly monodisperse multilayered vesicles above a threshold polymer concentration.     

The sponge phase of a mixed surfactant system

We study the sponge phase of the mixed non-ionic/ionic surfactant system C14DMAO-TTAB-hexanol-brine. Our aim is to determine if this phase exists in this mixed system and if it preserves or changes its structure when the relative amount of the charged surfactant is increased in the mixture. SAXS, FFEM, and conductivity results show that for the same bilayer volume fraction the sponge phase preserves its global structure. We propose a method to determine the geometrical obstruction factor from electrical conductivity measurements in ionic sponge phases. Analysis of lamellar phases in the same system shows that the bilayer thickness increases when the ionic surfactant concentration is increased.     

Slow Reorganization of Small Phosphatidylcholine Vesicles upon Adsorption of Amphiphilic Polymers

Static or dynamic light scattering measurements were performed in parallel, on dilute mixtures of DPPC/DPPA vesicles (typical radius 60 nm) and hydrophobically modified polymers. This technique gave evidence of the slow kinetics involved in both the reorganization of an adsorbed polymer layer and the membrane breakage. Hours, or sometimes days, were required in order to follow the variation of both the hydrodynamic radius and the scattering intensity at intermediate stages. Images of the intermediate species were collected using freeze-fracture electron microscopy (FFEM). Comparison of different polymers (of varying molecular weight or structure) revealed the prime importance of hydrophobicity on the disruption of membranes. Although the presence of a few percent of pendant alkyl chains along the polymer backbone induced adsorption to membranes, only the association with the more hydrophobic ones (>25 mol% of pendant octyl groups) resulted in small mixed objects of micellar size (radius about 10 nm). The drop of the mean radius of intermediate structures formed upon the vesicle breakage was also sensitive to temperature. A tentative mechanism was proposed on the basis of kinetics and FFEM studies. Copyright 2001 Academic Press.     

Shear-induced permeation and fusion of lipid vesicles

This paper introduces a novel approach to controlling membrane permeability in free unilamellar vesicles using shearing in the presence of a detergent with a large head-group to tune pore formation. Such shear-induced permeation could offer a simple means of postencapsulating bioactive molecules to prepare vesicle vectors for drug delivery. Using UV absorption, fluorescence emission, dynamic light scattering, and electron microscopy, we investigated the membrane permeability and the morphology of unilamellar lipid vesicles (diameter in the range 50-400 nm) subjected to a shear stress in the presence of a small amount of nonionic surfactant (Brij 76). Shear-induced leakage and fusion events were observed. We analyzed the significance of the vesicle size, the shear rate, and the surfactant-to-lipid ratio for the observed phenomena. The present approach is evaluated for postloading of preformed vesicles.