Bile salt-soluble amphiphile micelles

Since 1970, little work has been published on this subject. A kinetic dialysis study has been employed to determine the CMC and composition of mixed bile salt 

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On the basis of surface and bulk interaction with water. Small [85] classified bile acids as insoluble amphiphiles and bile salts as soluble amphiphiles. On account of the undissociated carboxylic acid group, the aqueous solubility of bile acids is limited [35] in contrast, many bile salts have high aqueous solubilities as monomers [33] and, in addition, their aqueous solubilities are greatly enhanced by the formation of micelles [5,6]. Because many bile salts are weak electrolytes, their ionization and solubility properties are more complicated than those of simple inorganic or organic electrolytes [5,35]. For example, the p/Tj, values of bile acids in water vary markedly as functions of bile salt concentration and, because micelles formed by the A (anionic) species can solubilize the HA (acid) species [5,35], the equilibrium precipitation pH values of bile acids also vary as functions of bile salt concentration. Finally, certain bile salts are characterized by insolubility at ambient temperatures [2,5,6,86,87], only becoming soluble as micelles at elevated temperatures (the critical micellar temperature) [6]. 

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. 

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. 

The impact of different surfactants (SDS, DOSS, CTAB and hexadimethrine bromide, bile salts °), nonionic and mixed micelles, and additives (neutral and anionic CDs," " tetraalkylammonium salts, organic solvents in EKC separations has been demonstrated with phenol test mixtures. In addition, phenols have been chosen to introduce the applicability of more exotic EKC secondary phases such as SDS modified by bovine serum albumin, water-soluble calixarene, " starburstdendrimers, " " cationic replaceable polymeric phases, ionenes, amphiphilic block copolymers,polyelectrolye complexes,and liposome-coated capillaries. The separation of phenols of environmental interest as well as the sources and transformations of chlorophenols in the natural environment have been revised. Examples of the investigation of phenols by EKC methodologies in aquatic systems, soil," " and gas phase are compiled in Table 31.3. Figure 31.3 illustrates the electromigration separation of phenols by both CZE and EKC modes. 

Simple micelles, composed only of bile salts, have a limited capacity to solubilize cholesterol. With taurocholate for example, one molecule of cholesterol is solubilized by 25 molecules of bile salt, while addition of a monoglyceride to the preparation essentially doubles the solubilization of cholesterol[17]. Obviously, the participation of additional amphipaths and amphiphiles, such as phospholipids and fatty acids, in the micellar structure causes dramatic increases in sterol solubility (from 100-1000 fold)[48]. 

Bile contains three amphiphiles (cholesterol, lecithin and bile salts) assembled in mixed micelles. These greatly increase water-solubility of cholesterol (usually very low about 70-80 nM). If excess cholesterol is present, the solubilizing capacity of the micelles is exceeded and supersaturation reached nucleation of cholesterol molecules can occur with formation of cholesterol mono-hydrate crystals and stones[8]. Only ChM is found in gallstones and its dissolution rate is slower than anhydrous cholesterol[9]. 

Bile salts are soluble amphiphiles forming simple micelles in water the capacity to solubilize CH is increased (about 4 times) in the presence of lecithin (mixed micelles)[8]. The solubilization capacity of mixed micelles for cholesterol increases with increasing total lipid concentration, temperature, and Lec/BS molar ratio[12]. 

Fatty acids are in the form of soluble amphiphiles since the pH in the proximal part of the small intestine, where digestion takes place, has risen from the acid values in the stomach to around 5.8-6.5. The partition of long chain fatty acids into the micellar phase is favoured by the gradual increase in pH that occurs in the luminal contents as they pass into the more distal parts of the small intestine. Bile salts are also incorporated into micelles. The presence of these soluble amphiphiles helps to incorporate very... 

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