Bile salt micelles

While the detergent molecule has a clear-cut polarity between its hydrophilic and lipophilic parts, the lipophilic part of the bile salt is confined to one side of the steroid nucleus, the other side being spiked with hydrophilic OH groups. In the small primary micelle, bile salt... 

If the solutes are planar, such as a steroid [23] or macrocyclic antibiotic [24], try a bile salt micelle. Bile salts can be used in conjunction with SDS as well [25],... 

Bile salts act as "detergents" in nature to maintain insoluble (fat-soluble) compounds in water solution. The bile salts form mixed micelles that consist of amphipathic bile salt molecules surrounding the lipophilic (fal-soJublc) molecules. The hydrophilic ends of the amphipathic molecules face outward, forming a lipophilic environment in the interior of the micelle. Bile salt molecules contain acid groups, such as carboxyl and sulfonyl groups, that usually are ionized under physiological conditions. 

The structure of cholic acid helps us understand how bile salts such as sodium tauro cholate promote the transport of lipids through a water rich environment The bot tom face of the molecule bears all of the polar groups and the top face is exclusively hydrocarbon like Bile salts emulsify fats by forming micelles m which the fats are on the inside and the bile salts are on the outside The hydrophobic face of the bile salt associates with the fat that is inside the micelle the hydrophilic face is m contact with water on the outside... 

Bde salts, cholesterol, phosphoHpids, and other minor components are secreted by the Hver. Bile salts serve three significant physiological functions. The hydrophilic carboxylate group, which is attached via an alkyl chain to the hydrophobic steroid skeleton, allows the bile salts to form water-soluble micelles with cholesterol and phosphoHpids in the bile. These micelles assist in the solvation of cholesterol. By solvating cholesterol, bile salts contribute to the homeostatic regulation of the amount of cholesterol in the whole body. Bile salts are also necessary for the intestinal absorption of dietary fats and fat-soluble vitamins (24—26). 

FIGURE 24.4 In the small intestine, fatty acids combine with bile salts in mixed micelles, which deliver fatty acids to epithelial cells that cover the intestinal villi. Triacylglycerols are formed within the epithelial cells. 

Irrespective of the physical form of the carotenoid in the plant tissue it needs to be dissolved directly into the bulk lipid phase (emulsion) and then into the mixed micelles formed from the emulsion droplets by the action of lipases and bile. Alternatively it can dissolve directly into the mixed micelles. The micelles then diffuse through the unstirred water layer covering the brush border of the enterocytes and dissociate, and the components are then absorbed. Although lipid absorption at this point is essentially complete, bile salts and sterols (cholesterol) may not be fully absorbed and are not wholly recovered more distally, some being lost into the large intestine. It is not known whether carotenoids incorporated into mixed micelles are fully or only partially absorbed. 

In the in vitro digestion method, the compound of interest is transferred from the food matrix to a bile salt micelle suspension that simulates the in vivo digestion process. This in vitro digestion procedure was first developed to estimate iron availability from meals and since then has been modified and applied to studying carotenoid bioaccessibility from various food matrices. This approach assesses the bioaccessibility of the compound from a certain meal before it is presented to and taken up by intestinal cells. 

Clothier, Jr., J. G. and Tomellini, S. A., Chiral separation of veraprimil and related componds using micellar electrokinetic capillary chromatography with mixed micells of bile salt and polyoxyethylene ethers,. Chromatogr. A, 712, 179,1996. 

Certain surface-active compounds [499], when dissolved in water under conditions of saturation, form self-associated aggregates [39,486-488] or micelles [39,485], which can interfere with the determination of the true aqueous solubility and the pKa of the compound. When the compounds are very sparingly soluble in water, additives can be used to enhance the rate of dissolution [494,495], One can consider DMSO used in this sense. However, the presence of these solvents can in some cases interfere with the determination of the true aqueous solubility. If measurements are done in the presence of simple surfactants [500], bile salts [501], complexing agents such as cyclodextrins [489 191,493], or ion-pair-forming counterions [492], extensive considerations need to be applied in attempting to extract the true aqueous solubility from the data. Such corrective measures are described below. 

An alternative method to overcome the solubility problem mentioned in the last section is to use bile salts to solubilize lipophilic molecules in the donor wells. Figure 7.51 shows a plot of relative permeability (Pe without bildPe with bile) versus membrane retention, which is related to lipophilicity (Section 7.7.2). As the plot shows, the most lipophilic molecules (carvedilol, propranolol, and verapamil) have attenuated permeabilities (by a factor of 3 in the case of carvedilol). The effective partition coefficient between the PAMPA membrane phase and the aqueous phase containing bile salt micelles [577] is expected to be lower for lipophilic molecules, which should result in lower Pe values. This is evident in the figure. 

Highly insoluble molecules are in part transported in the GIT by partitioning into the mixed micelles injected into the lumen from the biliary duct in the duodenum (Fig. 2.3). Mixed micelles consist of a 4 1 mixture of bile salts and phospholipids (Fig. 7.13). In contrast, at the point of absorption in the BBB, highly insoluble molecules are transported by serum proteins. This distinction is expected to be important in in vitro assay modeling. The use of simulated intestinal fluids is appealing. 

Penetration enhancers are low molecular weight compounds that can increase the absorption of poorly absorbed hydrophilic drugs such as peptides and proteins from the nasal, buccal, oral, rectal, and vaginal routes of administration [186], Chelators, bile salts, surfactants, and fatty acids are some examples of penetration enhancers that have been widely tested [186], The precise mechanisms by which these enhancers increase drug penetration are largely unknown. Bile salts, for instance, have been shown to increase the transport of lipophilic cholesterol [187] as well as the pore size of the epithelium [188], indicating enhancement in both transcellular and paracellular transport. Bile salts are known to break down mucus [189], form micelles [190], extract membrane proteins [191], and chelate ions [192], While breakdown of mucus, formation of micelles, and lipid extraction may have contributed predominantly to the bile salt-induced enhancement of transcellular transport, chelation of ions possibly accounts for their effect on the paracellular pathway. In addition to their lack of specificity in enhancing mem-... 

Morimoto et al. [33] demonstrated that the ocular absorption of hydrophilic compounds over a wide range of molecular weights could be increased by 2 and 10 mM sodium taurocholate and sodium taurodeoxycholate in a dose-dependent manner. The compounds were glutathione (307 Da), 6-carboxyfluorescein (376 Da), FTTC-dextran (4 kDa), and insulin (5.7 kDa). Of the two bile salts, sodium taurodeoxycholate was more effective. At 10 mM, this bile salt increased the permeability of 6-carboxyfluorescein from 0.02% to 11%, glutathione from 0.08% to 6%, FITC-dextran from 0% to 0.07%, and insulin from 0.06% to 3.8%. Sodium taurocholate, on the other hand, increased the permeability to 0.13%, 0.38%, 0.0011%, and 0.14%, respectively. Taurodeoxycholate was more effective than taurocholate in the nasal epithelium as well [202], This difference in activities can possibly be attributed to their micelle-forming capability, which is higher for taurodeoxycholate, a dihydroxy bile salt [190],... 

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