Lipid-water systems

Luzzati V, Tardieu A, Gulik-Krzywicki T, Rivas E and Reiss-Flusson F 1968 Structure of the cubic phases of lipid-water systems Nature 220 485-8... 

In this work we will focus on the use of the cubic phase as a delivery system for oligopeptides - Desmopressin, Lysine Vasopressin, Somatostatin and the Renin inhibitor H214/03. The amino acid sequences of these peptides are given in Table I. The work focuses on the cubic phase as a subcutaneous or intramuscular depot for extended release of peptide drugs, and as a vehicle for peptide uptake in the Gl-tract. Several examples of how the peptide drugs interact with this lipid-water system will be given in terms of phase behaviour, peptide self-diffusion, in vitro and in vivo release kinetics, and the ability of the cubic phase to protect peptides from enzymatic degradation in vitro. Part of this work has been described elsewhere (4-6). 

It should be pointed out that cubic phases, such as the one discussed in this work, frequently occur in lipid-water systems (77), and the concept of using cubic phases as drug vehicles is therefore not limited to the use of monoolein only. From a toxicological stand-point, it is tempting to try to use membrane lipids, such as phospholipids, instead of monoolein for parenteral depot preparations (18-20). 

Gruszecki, W. I. 1991. Violaxanthin and zeaxanthin aggregation in lipid-water system. Stud. Biophys. 139 95-101. 

Chiou, C. T. (1985) Partition coefficients of organic compounds in lipid-water systems and correlations with fish bioconcentration factors. Environ. Sci. Technol. 19, 57-62. 

V. Luzzati, in D. Chapman (Ed.), Biological Membranes Physical Fact and Function, X-Ray Diffraction Studies of Lipid-Water Systems, Academic Press, London, 1968. 

The present knowledge about molecular organization in lyotropic liquid crystalline phases is summarized. Particular attention is given to biologicaly relevant structures in lipid-water systems and to lipid-protein interactions. "New findings are presented on stable phases (gel type) that have ordered lipid layers and high water content. Furthermore, electrical properties of various lipid structures are discussed. A simple model of l/l noise in nerve membranes is presented as an example of interaction between structural and electrical properties of lipids and lipidr-protein complexes. 

Figure 6. Cubic structures in lipid-water systems based on space-filling polyhedra. The data from the monoglyceride-water cubic phases fit with the body-centered structure to the right.

Some measurements were also made on lamellar tetradecyl amine-water systems (see section on The Gel State in Lipid-Water Systems) with 88-95% water using the method described in Ref. 37. In this case, the water layer was about 1500-1600 A thick, and no counterions were present. Conductivity in the lamellar region is therefore expected to be caused by protons jumping between the amine groups of the lipid. Figure... 

Interest in thermotropic liquid crystals has focussed mainly on macroscopic properties studies relating these properties to the microscopic molecular order are new. Lyotropic liquid crystals, e.g. lipid-water systems, however, are better known from a microscopic point of view. We detail the descriptions of chain flexibility that were obtained from recent DMR experiments on deuterated soap molecules. Models were developed, and most chain deformations appear to result from intramolecular isomeric rotations that are compatible with intermodular steric hindrance. The characteristic times of chain motions can be estimated from earlier proton resonance experiments. There is a possibility of collective motions in the bilayer. The biological relevance of these findings is considered briefly. Recent similar DMR studies of thermotropic liquid crystals also suggest some molecular flexibility. 

Most of our proton NMR studies on lipid-water systems were made in P. Rigny s laboratory (Division de Chimie, C.E.N. Saclay). Many of the ideas that are expressed here were discussed under his critical and stimulating guidance. 

Seddon JM, Templer RH (1995) Polymorphism of lipid-water systems. In Lipowsky R, Sackmann E (eds) Handbook of biological physics. Elsevier Science, Amsterdam, pp 97-160... 

Chiou, C.T., Block, J.B. (1986) Parameters affecting the partition coefficient of organic compounds in solvent-water and lipid-water systems. In Partition Coefficient, Determination and Estimation. W.J. Dunn III, J.H. Block, R.S. Pearlman, Eds., pp. 36-60. Pergamon Press, New York. 

Silyl groups, which tend to increase lipid solubility, may be used as a substitute for alkyl branching in space-filling groups. Direct substitution of a silicon atom for a carbon atom increases the hydrophobic character of a compound, even without the addition of more alkyl groups. Table III lists the relative partition coefficients of two pairs of carbon and silicon compounds in octanol-water, a system used to approximate the lipid-water system within an organism. As may be seen from the table, the silicon compounds are two to five times more soluble in the octanol phase this effect falls off with an increasing number of carbon atoms in the parent structure (36). 

In addition, the reversibility of phase transition in lipid-water systems has been studied [30]. It was observed that the relaxation times in the transition region and the lifetimes of the metastable phases are similar, and sometimes significantly longer than the times characteristic of the biomembrane processes. The question arises as to the physiological significance of the equilibration that occurs a long time after lipid phase transition. 

In a lipid/water system, the thickness of the bilayers is constant, and the unbinding transition can occur, in principle, by varying the Hamaker constant or temperature.22 For lyotropic lamellar liquid crystals, hyperswelling in a liquid of one kind might also occur if the lamellae of the other kind are thin enough and hence unbound. However, thin lamellae might lead to a positive contribution to the free energy (since the repulsive forces overcome at short distances the van der Waals attraction), and hence the lamellar phase can become unstable. 

Luzatti, W. "X-ray Diffraction Studies of Lipid-water Systems" (Biological Membranes, Physical Fact and Function), Chapman, C., Ed. Academic Press New York, 1968 pp. 71-123. 

Champan, D., Urbina, J., and Keough, K. M. (1974), Studies of lipid water systems using differential scanning calorimetry,/. Biol. Chem., 249(8), 2512-2521. 

Analysis of the results and comparison with the lipid phase transition observed iq the bulk lipid/water systems allows to conclude that the lowest temperature during heating at which measurable diffusion occurred correlates with the onset of formation of the lamellar Ln liquid crystalline phase of the given phospholipid. Therefore, the data support a correlation between the surface and bulk phase transitions. This was confirmed in recent studies where the lipid surface phase transition was successfully measured for the first time in foam film by independent means involving the detailed investigations of the temperature dependences of the W(C) curve for the foam film and its thickness. 

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