Micelles deoxycholate

Certain compounds are known to achieve higher absorption rates from the GI tract if they are taken with food, and this observation has been linked to their solubilization by bile salts [74], Bile salts, especially those of cholic and deoxycholic acids, have been used to solubilize steroid hormones [75], antibiotics [76], and nonsteroidal antiinflammatory drugs [77]. For example, amphotericin B (an antifungal agent) has been solubilized for parenteral use in micelles composed of sodium desoxycholate [78], As illustrated in Fig. 11, the degree of solubilization of carbamazepine by sodium desoxycholate is minimal below the critical micelle concentration but increases rapidly above this value [79]. At sufficiently high concentrations, when the micelles become saturated in carb-amezepine, the apparent solubility reaches a limiting value approximately seven times the true aqueous solubility in the absence of desoxycholate. 

AmB has very low bioavailability by the oral route and so has to be given intravenously for the treatment of systemic infections. Due to its insolubility in aqueous media, the traditional formulation is mixed micelles with deoxycholate (Fungizone , Bristol-Myers Squibb). However, the micelles... 

A and B are in cis position relative to each other (see p. 54). One to three hydroxyl groups (in a position) are found in the steroid core at positions 3, 7, and 12. Bile acids keep bile cholesterol in a soluble state as micelles and promote the digestion of lipids in the intestine (see p.270). Cholic add and cheno-deoxychoMc acid are primary bile acids that are formed by the liver. Their dehydroxylation at C-7 by microorganisms from the intestinal flora gives rise to the secondary bile acids lithocholic acid and deoxycholic acid. 

AmB is a poorly water-soluble drug that is currently formulated with the bile salt deoxycholate (Fungizoni5). This formulation induces hemolysis and slowed release of AmB is shown to prevent this toxic side effect. In addition, Yu et al. investigated the effect of freeze-drying and reconstitution on the micelles. 

It was found that unloaded PEBPBLA micelles cause no hemolysis, even at a level of 0.70 mg/mL. PECb-PBLA has an extremely low critical micelle concentration (Kwon et al., 1993), and thus, there is little monomeric PBEPBLA for the lysis of lipid bilayer membranes. In addition, PEO-bPBLA micelles may break apart slowly to monomers. The lack of hemolytic activity of PEO-bPBLA contrasts strongly with other amphiphiles used for drug solubilization and intravenous drug administration. Sodium deoxycholate causes 100% hemolysis at a level of 0.32 mg/mL. This is due to disruption of lipid bilayer membranes of red blood cells. 

Bile salts sodium deoxycholate sodium glycocholate sodium fusidate sodium taurodihydrofusidate denaturation of proteins decrease of mucus viscosity decrease of peptidase activity solubilization of peptides formation of reversed micelles... 

Bile salts Sodium deoxycholate Sodium glycocholate Sodium taurocholate Formation of reverse micelles, solubilization of proteins/peptides Removal of epithelial cells and formation of transient pores Inhibition of proteolytic activity Reduction of mucus viscosity... 

Particularly efficient solubilizing agents of the bile acid family are the salts of deoxycholic acid 6". Their complexes with water-insoluble compounds are called choleic acids . The aggregation number of deoxycholic acid (DCA) in distilled water is approximately 10-12 ( primary micelles ) and rises to about 100 ( secondary micelles ) in more concentrated solutions and/or after addition of electrolytes to primary micelles. The cmc of primary micelles lies in the range of 1-5 x 10 mol/L. Less polar cholic acids are in general much better... 

Figure 3.11 Schematic model of a micelle consisting of 12 molecules of the rigid facial amphiphile deoxycholic acid. The polar surface is at the concave inside apolar molecules are solubilized on the outer surface.

Neutral steroidal glucoside surfactants, such as N,N-bis-(3-D-gluconamidopropyl)-cholamide (Big CHAP) and A,A-bis-(3-D-gluconamidopropyl)-deoxychola-mide (Deoxy Big CHAP), which contain a cholic or deoxycholic acid moiety, respectively, have been introduced for use as chiral pseudo-stationary phases in MEKC. By using a borate buffer under basic conditions, these surfactant micelles could be charged via borate complexation. Some binaphthyl enantiomers, Troger s base, phenoxy acid herbicide, and Dns-DL-AAs were enantioseparated. 

Enthalpy of Micelle Formation of Mixed Sodium Dodecyl Sulfate and Sodium Deoxycholate Systems in Aqueous Media... 

The enthalpy of micelle formation of various mixed sodium dodecylsulfate (NaDDS) and sodium deoxycholate (NaDOC) systems was measured by calorimeter In aqueous systems. The heat of micelle formation, AH, showed a maximum around NaDDS NaDOC molar ratio 1. These data are analyzed In comparison to the aggregation number of mixed micelles and the second virial coefficient, Bg. 

This study is a continuation of our previous investigations, in which the aggregation phenomena of surfactant molecules (amphiphiles) in aqueous media to form micelles above the critical micelle concentration (c.m.c.) has been described based on different physical methods (11-15). In the current literature, the number of studies where mixed micelles have been investigated is scarcer than for pure micelles (i.e., mono-component). Further, in this study we report various themodynamlc data on the mixed micelle system, e.g., ci H25soi4Na (NaDDS) and sodium deoxycholate (NaDOC), enthalpy of micelle formation (by calorimetry), and aggregation number and second virial coefficient (by membrane osmometry) (1 6). 

Polycyclic aromatic hydrocarbons (PAHs) have been separated by MEKC using a double alkyl chain di(2-ethylhexyl) phosphate as anionic micellar pseudostationary phase. Phospholipids have been separated from soya lecithins by MEKC, deoxycholic acid being used for micelle formation. Separation was tested according to solvent polarity and column temperature, with a high n-propanol concentration and a column temperature of 15 °C being ideal. Online MEKC/MS with electrospray ionisation, and atmospheric-pressure Cl, interfaces have been used in the separation and detection of standard compounds, including tetraphenylphosphonium chloride. ... 

This means that for 1-alcohols, CH3-(CH2) -CH20H, the A parameter (n = 0) is in principle the AG" value of ethanol, and for hydrocarbons the A value is AG" of ethane. Values of the A and B parameters for the varions systems are presented in Table 6.8. Basically all systems fit Equation 6.28 well, and it also turns out that the B parameter is surprisingly constant for nearly all systems. Exceptions are phenylalcohols in sodinm deoxycholate micelles and primary alcohols in lithium perfluoro-octane-sulfonate. The average value of the B parameter for all other systems is -2.48 0.06 kJ/mol... 

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