Monoolein-water system

Oligopeptides in the Monoolein-Water System. Most oligopeptides are amphiphilic molecules, i.e. they have both hydrophilic and lipophilic characteristics,... 

Caboi, F., Amico, G.S., Pitzalis, P., Monduzzi, M., Nylander, T., and Larsson, K. (2001). Addition of hydrophilie and lipophilic compounds of biological relevance to the monoolein-water system. 1. Phase behavior. Chem. Phys. Lipids. 109,47-62. 

Results for the monoolein/water system give mutual diffusion coefficients ranging from 0.7-1.5 x 10-6 cm/s in the fluid isotropic, lamellar liquid crystal and cubic phases ([55a], Fig.7).These values are up to an order of magnitude lower than literature values of the self diffusion coefficients determined by pulsed field gradient NMR for this same system [96],... 

Monoolein, a common food emulsifier, gives rise to a bicontinuous cubic liquid crystalline phase when added to water, as illustrated in Fig. 4. If a triglyceride oil is introduced into the monoolein-water system, a microemulsion (L2) phase is formed above about 10 wtVo oil as discussed in Sect. II.B. If lecithin is added, the cubic phase is preserved up to about 30 wt% lecithin, beyond which a lamellar (L ) phase is formed [8]. Adding a bile salt, e.g., sodium taurocholate, in sufficient amount will convert the cubic phase to a micellar solution (L,) [9]. 

The effect of adding various lipids to monoolein was discussed above. These lipids are soluble in either water (bile salt) or oil (triglyceride) or hardly soluble at all (lecithin). If a substance that is soluble in both water and oil, e.g., propylene glycol, is added to the monoolein-water system, the cubic liquid crystal undergoes a transition to a sponge or L3 phase [13], as shown in Fig. 5. The structure of the sponge phase has been described as a melted bicontinuous cubic phase [14]. 

Fig. 12.5 Temperature-composition phase diagram of the monoolein/water system (up to 50 wt% water). A cartoon representation of the various phase states is included in which colored zones represent water. The mesophases are as follows Lc-crystalline lamellar, La-lamellar, la3d-gyroid inverted bicontinuous cubic, Pn3m-primitive inverted bicontinuous cubic, Hn-inverted hexagonal, and Fl-reverse micelles fluid phases (Taken from [8])...

As an example of the effects of an amphiphilic drug on the structure of surfactant self-assemblies. Figure 1.4 shows part of the phase diagram of monoolein, water, lidocaine base and licocaine-HCl (21). As can be seen, the cubic phase (c) formed by the monoolein-water system transforms into a lamellar liquid crystalline phase on addition of lidocaine-HCl, whereas it transforms into a reversed hexagonal or reversed micellar phase on addition of the lidocaine base. Based on X-ray data, it was inferred that the cubic phase of the monoolein-water system had a slightly reversed curvature (critical packing parameter about 1.2). Thus, on addition of the... 

Figure 1.13, Phase diagram of the monoolein/water system. The cubic phases are denoted G (the gyroid type) and D (the diamond type). The arrows indicate two different means to reach an in situ formation of a bicontinuous cubic phase, i.e. through increasing the temperature of a lamellar phase at a fixed composition (A), and through dilution with water of a reversed micellar phase at a fixed temperature (B) (data from ref. (266))...

Engstrom, S. and Engstrom, L., Phase behaviour of the lidocaine-monoolein-water system, Int. J. Pharm., 79, 113-122 (1992). 

Engstrom, S., Ljusberg-Wahren, H. and Gustafsson, A., Bioadhesive properties of the monoolein-water system, Pharm. Technol. Eiir., Publication Number 0063, (February 1995). 

Qiu, H. Caffrey, M. (2000). The phase diagram of the monoolein/ water system metastability and equilibrimn aspects. Biomaterials, 21(3), 223-34. 

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). 

Cubic phases are also unique in their ability to accommodate proteins as compared to other lipid-water phases. A wide range of globular proteins with molecular weights 5,000-150,000 are known to form cubic phases when mixed with lipids and water. So far few single ternary lipid-protein-water phase diagrams have been completely determined [7], [13] one system that has been looked at is that of monoolein-water-lysoz5one. Protein incorporation results in increased water swelling, and all three phases, Cp, Cd and CG/ occur. The protein molecules are located in the water channel systems and retain their native structure. This has been proved by thermal analysis of the phase, and measurements of enzymatic activity [7]. 

The phase behavior of the binary MLO-water system is similar to that of the well-studied monoglyceride monoolein (MO) [98]. Both amphiphilic lipids have cA-configrtration that introduces a kink in their acyl chain [79]. These lipids are widely used in food industry as they are specified as GRAS (generally recognized as safe). They are subject to enzymatic lipolysis in a wide range of tissues and therefore are considered biocompatible and biodegradable materials [94]. 

A continuous lipidic cubic phase is obtained by mixing a long-chain lipid such as monoolein with a small amount of water. The result is a highly viscous state where the lipids are packed in curved continuous bilayers extending in three dimensions and which are interpenetrated by communicating aqueous channels. Crystallization of incorporated proteins starts inside the lipid phase and growth is achieved by lateral diffusion of the protein molecules to the nucleation sites. This system has recently been used to obtain three-dimensional crystals 20 x 20 x 8 pm in size of the membrane protein bacteriorhodopsin, which diffracted to 2 A resolution using a microfocus beam at the European Synchrotron Radiation Facility. 

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