Phase lecithin cholesterol

Khovidhunkit W, Shigenaga JK, Moser AH, Feingold KR, Grunfeld C. Cholesterol efflux by acute-phase high density lipoprotein Role of lecithin Cholesterol acyltransfer-ase. J Lipid Res 2001 42 967-975. 

The positive heats of mixing for lecithin-cholesterol mixtures indicate that interactions between unlike molecules are smaller than the interactions between like molecules, i.e., the hydrocarbon chain interactions with cholesterol are smaller than in each of the pure phases. If the excess heats of mixing become large enough, phase separation will occur. It may occur when the surface pressure is increased (i.e., as the films are compressed). The point at which phase separation occurs is difficult to predict, measure, or detect however, evidence of phase separation can be deduced from the following experiment. If excess amounts of two lipids are placed in water, the equilibrium surface pressure should reflect whether the surface film is a mixture. According to the phase rule (11,12, 13,14), if two bulk lipid phases are present, only one surface phase can be present at the air—water surface. Thus the composition of the equi-... 

In an earlier review [3], mixed micelles formed by bile salts were classified into those with (i) non-polar lipids (e.g., linear or cyclic hydrocarbons) (ii) insoluble amphiphiles (e.g., cholesterol, protonated fatty acids, etc.) (iii) insoluble swelling amphiphiles (e.g., phospholipids, monoglycerides, acid soaps ) and (iv) soluble amphiphiles (e.g., mixtures of bile salts with themselves, with soaps and with detergents) and the literature up to that date (1970) was critically summarized. Much recent work has appeared in all of these areas, but the most significant is the dramatic advances that have taken place in our understanding of the structure, size, shape, equilibria, and thermodynamics of bile salt-lecithin [16,18,28,29,99-102,127, 144,218,223,231-238] and bile salt-lecithin-cholesterol [238,239] micelles which are of crucial importance to the solubihty of cholesterol in bile [1]. This section briefly surveys recent results on the above subclasses. Information on solubilization, solubilization capacities or phase equilibria of binary, ternary or quaternary systems or structures of liquid crystalline phases can be found in several excellent reviews [5,85,207,208,210,211,213,216,217] and, where relevant, have been referred to earlier. 

Bile is a mixed micellar solution of bile salt-lecithin-cholesterol which on dilution forms aggregates of much larger size than micelles indicating the formation at the phase limits of liposome-like bodies [9]. In intestinal content during lipid digestion in man, saturated mixed micelles and vesicles or liposomes containing the... 

In the lumen of the small intestine, dietary fat does not only meet bile salt but the much more complex bile in which bile salts are about half saturated with lecithin in a mixed micellar system of bile salt-lecithin-cholesterol. On dilution in the intestinal content, the micelles grow in size as the phase limit is approached and large disk-like micelles form which fold into vesicles [49]. These changes are due to the phase transition that occurs when the bile salt concentration is decreased and the solubility limit for lecithin in the mixed micelles is exceeded. The information is mostly derived from in vitro studies with model systems but most probably is applicable to the in vivo situation. What in fact takes place when the bile-derived lamellar bile salt-lecithin-cholesterol system meets the partly digested dietary fat can only be pictured. Most probably it involves an exchange of surface components, a continuous lipolysis at the interphase by pancreatic enzymes and the formation of amphiphilic products which go into different lamellar systems for further uptake by the enterocyte. Due to the relatively low bile salt concentration and the potentially high concentration of product phases in intestinal content early in fat digestion, the micellar and monomeric concentration of bile salt can be expected to be low but to increase towards the end of absorption. 

Surpuriya, V., and Higuchi, W.I. (1974) Enhancing Effect of Calcium Ions on Transport of Cholesterol from Aqueous Sodium Taurocholate-Lecithin Micellar Phase to Oil Phase, J. Pharm. Sci. 63,1325 1327. 

A. K. Soutar, H. J. Pownall, A. S. Hu, and L. C. Smith, Phase Transitions in Bilamellar Vesicles. Measurements by Pyrene Excimer Fluorescence and Effect on Transacylation by Lecithin Cholesterol Acyltransferase, Biochemistry 13, 2828-2836 (1974). 

Monolayer phase diagrams of lecithin/phos-phatidic acid and lecithin/cholesterol and cholesterol/ phosphatidic acid were also reported by Albrecht et al. (1981). An interesting feature in these binary monolayer systems is the indication of a lecithin/ phosphatidic acid 1 1 complex with crystalline chains. 

Leupeptide (the tripeptide inhibitor of proteolytic enzymes) can be delivered into the brain by means of liposomes obtained by reverse phase evaporation from a mixture of lecithine, cholesterol... 

STRUCTURAL PROPERTIES OF A LECITHIN-CHOLESTEROL SYSTEM RIPPLE STRUCTURE AND PHASE DIAGRAM... 

Lecithin cholesterol acyltransferase, LCAT, is the second enzyme of major importance in the enzymic phase of lipoprotein metabolism. Cholesteryl ester formation by this enzyme significantly changes the dynamics of the plasma cholesterol pool. Unlike the spontaneous rapid equilibration of cholesterol between lipoproteins. 

The important quaternary system of conjugate bile acids-watcr— lecithin-cholesterol has been studied by Small and Bouiges (1966) and Small el al. (1966a,b) and they have clarified the previously known fact (Spanner and Baumann, 1932 Isaksson, 1953-1964) that the high solubility of cholesterol in bile is possible only because of the cooperative solvent effects of conjugated bile acids and lecithin. However, only a certain amount of cholesterol can be dissolved in a mixed micellar phase of bile acids-water-leeithin. At low lecithin-bile acid ratios excess of cho-lesteral will appear in a crystalline form and at high lecithin-bile acid ratios in a liquid crystalline phase. 

For mixtures of lecithin plus Na cholate it appears possible to infer the molecular arrangement in the dispersed micelles from the most likely structure of the liquid crystalline phase suggested by x-ray analysis. However, there are cases where dispersion is not possible because neither component is sufficiently hydrophilic to be dispersed even when alone in water. This is shown by the association of cholesterol and lecithin in the presence of water. The ternary diagram of Figure 4 is relative to these systems. Here only the lamellar liquid crystalline phase is obtained (region 1< in Figure 4). This phase is already given by lecithin alone, which can absorb up to 55% water. Cholesterol can be incorporated within this lamellar phase up to the proportion of one molecule of choles-... 

Figure 4. Ternary phase diagram for system lecithin (L), cholesterol (Choi), and water (W)...

This lamellar phase is formed of alternate sheets of lipid and water. The lipidic sheets containing the lecithin and the cholesterol are made of two superposed layers of oriented molecules. Each of these two monolayers is mixed and consists of lecithin and cholesterol molecules arranged side by side with their paraffinic ends turned toward the inside of the sheet and their polar groups (phosphatidyl choline group for lecithin and hydroxyl group for the cholesterol) outward—i.e., toward the adjacent sheet of water. This constitution of each of the two mono-layers forming the lipidic sheet is in conformity with the conclusion arising from the study of mixed monolayers of cholesterol and lecithin spread on the free surface of water (1). 

Since cholesterol is an important component of many biological membranes mixtures of polymerizable lipids with this sterol are of great interest. In mixed monolayers of natural lipids with cholesterol a pronounced condensation effect , i.e. a reduction of the mean area per molecule of phospholipid is observed68. This influence of cholesterol on diacetylenic lecithin (18, n = 12), however, is not very significant (Fig. 32). Photopolymerization indicates phase separation in this system. Apparently due to the large hydrophobic interactions between the long hydrocarbon chains of... 

Composite emulsion as carrier of hydrophilic medicine for chemotherapy was prepared by adding albumin to the internal water phase and lecithin or cholesterol to the oil phase, thus obtaining a water-in-oil emulsion. This emulsion was then pressed through Millipore membrane into an external water phase to form a w/o/w multiple emulsion. Its advantages are high size uniformity and high storage stability [66]. 

At large surfactant concentrations emulsion films as well as foam films exhibit a layer-by-layer thinning (stratification) and metastable black films are formed [31,347,512], Such a behaviour has been reported for hydrocarbon films obtained from solutions of lecithin in either benzene or a mixture of chloroform and decane at concentration higher than 0.6-0.8% as well as in films from oxidised cholesterol in decane [31,512]. Manev et. al. [347] have reported stratification of O/W type emulsion films, toluene being added as a disperse phase, occurring within a surfactant (NaDoS) concentration range of 0.017-0.14 mol dm 3. The number of metastable states was 5-6. Compared to foam films of analogous composition, the respective emulsion films were thicker, due to the weaker intermolecular attraction and the stratification occurred at lower surfactant concentrations. 

Fig. 7, Phase diagram showing the physical state of all possible combinations of cholesterol, bile salts, and lecithin (expressed as mole percent) in aqueous solutions. The line AB represents the maximum amount of cholesterol, according to Admirand and Small (A2), which can be dissolved by any mixture of bile salts and lecithin. [From ref. (A2). Reproduced from The Journal of Clinical Investigation, 1968, 47, by copyright permission ofThe American Society for Clinical Investigation.]...

Thermodynamic parameters for the mixing of dimyristoyl lecithin (DML) and dioleoyl lecithin (DOL) with cholesterol (CHOL) in monolayers at the air-water interface were obtained by using equilibrium surface vapor pressures irv, a method first proposed by Adam and Jessop. Typically, irv was measured where the condensed film is in equilibrium with surface vapor (V < 0.1 0.001 dyne/cm) at 24.5°C this exceeded the transition temperature of gel liquid crystal for both DOL and DML. Surface solutions of DOL-CHOL and DML-CHOL are completely miscible over the entire range of mole fractions at these low surface pressures, but positive deviations from ideal solution behavior were observed. Activity coefficients of the components in the condensed surface solutions were greater than 1. The results indicate that at some elevated surface pressure, phase separation may occur. In studies of equilibrium spreading pressures with saturated aqueous solutions of DML, DOL, and CHOL only the phospholipid is present in the surface film. Thus at intermediate surface pressures, under equilibrium conditions (40 > tt > 0.1 dyne/cm), surface phase separation must occur. 

The dependence of the ttv values on the composition of the vapor and condensed states for DML-CHOL, DOL-CHOL, and DOL-DML mixtures is shown in Figure 6. The upper curve is the surface vapor pressure as a function of the mole fraction of the liquid-expanded film the lower curve is for the dependence of irv on the composition of the gaseous phase. Ideal mixing behavior is given by the linear dotted line which joins the 7ry° points for each of the pure compounds. In all cases there was complete miscibility of the components as represented by the continuous function of 7rv with x. In the cholesterol mixtures positive deviations from Raoult s law are observed for the mixture of lecithins, ideal mixing is observed. These results confirm those obtained with lipid mixtures—i.e., cholesterol mixed with liquid-expanded lipid films forms rion-ideal mixtures with positive deviations for mixtures of lipids which are in the same monolayer state, as in the case of the liquid-expanded DOL-DML mixtures, ideal mixing results (8). 

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