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PubMed2004

In vitro and in vivo transfection efficiency of a novel ultradeformable cationic liposome.

Cationic lipids have been often used as one of the major components in making most promising non-viral gene delivery systems, whereas sodium cholate, a surfactant so-called edge activator has been used in preparing ultradeformable and ultraflexible liposomes called Transfersomes. Using both a cationic lipid, DOTAP and sodium cholate, a novel formulation of ultradeformable cationic liposome (UCL) has been prepared. The average particle size of this formulation was approximately 80 nm. The physical and chemical stabilities at two different temperatures (4 degrees C and 20 degrees C) were also evaluated for 60 days. The ultradeformability of new formulation was also assessed, and it has been proved that the formulation is deformable. In vitro transfection efficiency of plasmid DNA/UCL was assessed by the expression of green fluorescent protein (GFP) in four cell lines, OVCAR-3 (human ovarian carcinoma cells), HepG2 (human hepatoma cells), H-1299 (human lung carcinoma cells) and T98G (human brain carcinoma cells). The optimal ratio of DNA to liposome for maximal transfection efficiency was 1:14 (w/w) in all the cell lines except for the human brain carcinoma cells. The same formulation was tested for in vivo transfection efficiency and its retention time within the organs by applying the DNA/UCL complexes on hair-removed dorsal skin of mice non-invasively. It was found that genes were transported into several organs for 6 days once applied on intact skin.

DNA↗
PubMed1999

Proteolytic enzymes as a limitation for pulmonary absorption of insulin: in vitro and in vivo investigations.

In vitro biodegradation of insulin in lung cytosol and subcellular pellets of normal and diabetic rats was investigated. Rat lung was homogenized and subcellular fractions were isolated by ultracentrifugation. Degradations of [125I]-insulin after incubation with lung cytosol or subcellular pellets was determined using the trichloroacetic acid method. The results show that insulin is highly degraded in cytosol and subcellular pellets. Cytosolic insulin degradation was strongly inhibited by bacitracin or sodium cholate. The degradation of insulin in the lung cytosol from diabetic rats was significantly less than from normal rat. The lung protease activity reached a maximum at pH 7.4. Enzyme inhibitors like bacitracin and sodium cholate noticeably enhanced the relative pharmacological bioavailability of insulin when given intratracheally with insulin to normal rats. Acidic insulin solutions (pH 3.0) had more pronounced hypoglycaemic effects than neutrol solution (pH 7.0). These in vitro and in vivo results suggest that the proteolytic enzymes in the lung limit pulmonary delivery of insulin. The coadministration of protease inhibitors would be a useful approach for improving the pulmonary absorption of insulin.

Absorption↗
PubMed2005

Remodeling of human plasma lipoproteins by detergent perturbation.

Detergent perturbation, the treatment of total human plasma lipoproteins (TLP) with sodium cholate and its subsequent removal, has been used to study lipoprotein dynamics and stability. At physiological TLP concentrations, detergent perturbation converts low-density lipoproteins (LDL) and high-density lipoproteins (HDL) to higher-particle weight species with the concomitant release of apo A-I but not apo A-II as a lipid-poor species. Detergent perturbation of isolated HDL also releases lipid-poor apo A-I and forms larger HDL species, whereas detergent perturbation of an isolated LDL has no effect on its size. A model is presented in which detergent perturbation induces transfer of PC from metastable HDL and LDL to mixed micelles with sodium cholate. The remaining LDL and HDL are unstable because of the loss of their surface components, phospholipid and/or apo A-I, and fuse to give larger LDL and HDL particles. These effects on HDL, i.e., PC transfer, apo A-I dissociation, and particle fusion, emulate the activity of human plasma phospholipid transfer protein. Thus, detergent perturbation is a new and potentially powerful method for determining lipoprotein stability, studying the mechanisms for remodeling of plasma lipoproteins, and preparing new forms of HDL and LDL with unique interactions with lipoprotein transporters and receptors.

Apolipoprotein A-I↗
PubMed2001

Enhancement of jejunal absorption of conjugated bile acid by neurotensin in rats.

BACKGROUND & AIMS: Release of neurotensin (NT) from intestines is markedly stimulated by ingested fat, and NT may facilitate lipid digestion and absorption through various actions that are not fully understood. Our recent finding that NT stimulates hepatic output of bile acids only when bile delivery to the intestine is maintained has led us to investigate the effects of NT on bile acid absorption in the rat small intestine. METHODS: We measured the effects of intravenous infusion of NT (3-10 pmol x kg(-1) x min(-1)) on biliary recovery of (3)H-taurocholate ((3)H-TC) and (3)H-cholate administered into proximal and distal intestines or into isolated intestinal segments in situ in biliary fistula rats. To further understand the underlying mechanisms involved, the effects of NT on intestinal absorption of (3)H-D-glucose, (3)H-leucine, (14)C-antipyrine, and (51)Cr-EDTA were investigated by monitoring the absorption of radioactivity into superior mesenteric venous blood. RESULTS: Infusion of NT, at doses that caused near physiologic increases in blood NT levels, increased biliary recovery of (3)H-TC from the jejunum (3.4-fold) and ileum (1.7-fold), but did not enhance absorption of (3)H-cholate. NT also facilitated transcellular uptake of (3)H-glucose and (3)H-leucine and increased paracellular uptake to (51)Cr-EDTA and (3)H-mannitol, but did not alter the absorption rate for (14)C-antipyrine. CONCLUSIONS: These results indicate that NT can exert a facilitative effect on intestinal bile acid absorption and return to liver. This effect of NT may involve increases in paracellular absorption and carrier-mediated transport by mechanisms not yet identified.

Animals↗
PubMed2002

Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol level and foam cell lesion size.

Inflammatory cytokines have been linked to atherosclerosis by using cell culture models and acute inflammation in animals. The goal of this study was to examine lipoprotein levels and early atherosclerosis in chronic animal models of altered IL-1 physiology by using mice with deficient or excess IL-1 receptor antagonist (IL-1ra). IL-1ra knockout C57BL/6J mice fed a cholesterol/cholate diet for 3 mo had a 3-fold decrease in non-high-density lipoprotein cholesterol and a trend toward increased foam-cell lesion area compared to wild-type littermate controls. IL-1ra transgenic/low-density lipoprotein receptor (LDLR) knockout mice fed a cholesterol-saturated fat diet for 10 wk showed a 40% increase in non-high-density lipoprotein cholesterol, consistent with the IL-1ra knockout data, although there was no change in lesion size. When these IL1-ra overexpressing transgenic mice on the LDLR knockout background were fed a high-cholesterol/high-fat diet containing cholate, however, a statistically significant 40% decrease in lesion area was observed compared to LDLR knockout mice lacking the transgene. By immunohistochemistry, IL-1ra was present in C57BL/6J and LDLR knockout aortae, absent in IL-1ra knockout aortae, and present at high levels in LDLR knockout/IL-1ra transgene aortae. In summary, IL-1ra tended to increase plasma lipoprotein levels and, when fed a cholate-containing diet, decrease foam-cell lesion size. These data demonstrate that in selected models of murine atherosclerosis, chronic IL-1ra depletion or overexpression has potentially important effects on lipoprotein metabolism and foam-cell lesion development.

Animals↗
PubMed2004

An active type IV secretion system encoded by the F plasmid sensitizes Escherichia coli to bile salts.

F(+) strains of Escherichia coli infected with donor-specific bacteriophage such as M13 are sensitive to bile salts. We show here that this sensitivity has two components. The first derives from secretion of bacteriophage particles through the cell envelope, but the second can be attributed to expression of the F genes required for the formation of conjugative (F) pili. The latter component was manifested as reduced or no growth of an F(+) strain in liquid medium containing bile salts at concentrations that had little or no effect on the isogenic F(-) strain or as a reduced plating efficiency of the F(+) strain on solid media; at 2% bile salts, plating efficiency was reduced 10(4)-fold. Strains with F or F-like R factors were consistently more sensitive to bile salts than isogenic, plasmid-free strains, but the quantitative effect of bile salts depended on both the plasmid and the strain. Sensitivity also depended on the bile salt, with conjugated bile salts (glycocholate and taurocholate) being less active than unconjugated bile salts (deoxycholate and cholate). F(+) cells were also more sensitive to sodium dodecyl sulfate than otherwise isogenic F(-) cells, suggesting a selectivity for amphipathic anions. A mutation in any but one F tra gene required for the assembly of F pili, including the traA gene encoding F pilin, substantially restored bile salt resistance, suggesting that bile salt sensitivity requires an active system for F pilin secretion. The exception was traW. A traW mutant was 100-fold more sensitive to cholate than the tra(+) strain but only marginally more sensitive to taurocholate or glycocholate. Bile salt sensitivity could not be attributed to a generalized change in the surface permeability of F(+) cells, as judged by the effects of hydrophilic and hydrophobic antibiotics and by leakage of periplasmic beta-lactamase into the medium.

Anti-Bacterial Agents↗
PubMedDate not supplied

Intestinal absorption of low molecular weight heparin in animals and human subjects.

INTRODUCTION: We had previously shown that the use of bile salts, which act as surfactants, facilitates the intestinal absorption of large molecules such as those of heparin and insulin. However, the bioavailability of unfractionated heparin (UFH) administered through the large intestine was low. The aim of the present study was to evaluate the absorption of low molecular weight heparin (LMWH) combined with bile salts through the gut mucosa in animals and human subjects. MATERIALS AND METHODS: LMWH (Fragmin, Kabi-Pharmacia, Stockholm) or UFH with or without sodium cholate (Sch) was administrated rectally in rats and healthy volunteers via a microenema. Absorption was estimated by the activated partial thromboplastin time (aPTT), the plasma anti-factor Xa activity and the plasma lipoprotein lipase (LPL) activation. RESULTS: In groups of 6 rats, LMWH at doses of 100--1,000 U with sodium cholate (10--20 mg/ml) was readily absorbed through the gut mucosa, as indicated by both, anti-factor Xa levels of up to 1 U/ml and a dose-dependent activation of LPL. The absorption was significantly superior to that of UFH with Sch or LMWH given without Sch (p < 0.001). The plasma anti-factor Xa levels in the 6 healthy volunteers who received a microenema containing 25,000 U of LMWH with 20 mg/ml of Sch were 0.38 U/ml at 15 min and 0.1 U/ml at 240 min. LPL activation and aPTT prolongation were also observed in these subjects. The plasma LMWH levels after rectal application were in the same range as those obtained after subcutaneous administration, however the elimination time (t 1/2) was shorter. There were no adverse reactions. CONCLUSIONS: Intestinal absorption of LMWH facilitated by Sch is both feasible and safe. A slow release formulation will be needed to prolong the plasma half-life.

Administration, Rectal↗
PubMed2001

Physicochemical properties of liposomes incorporating hydrochlorothiazide and chlorothiazide.

In an attempt to study the effect of hydrophobic drugs on liposome properties, multilamellar liposomes (MLV) consisting of phosphatidylcholine (PC) and incorporating chlorothiazide (CT) or hydrochlorothiazide (HCT), were prepared and characterized. Liposome size, surface charge, stability (in buffer, plasma and sodium cholate) and calcium-induced aggregation were studied for drug-incorporating liposomes and empty liposomes for comparison. Results show that drug incorporation affects liposome size, z-potential and stability in presence of buffer and plasma proteins. Indeed, drug-incorporating liposomes are slightly larger and have a negative surface charge, which increases with the amount of drug incorporated in the lipid membrane. The membrane integrity of drug incorporating liposomes (in absence and presence of plasma proteins) is significantly higher when compared with that of empty liposomes (for both drugs studied). On the contrary, vesicle membrane integrity in presence of sodium cholate and calcium induced vesicle aggregation, are not affected by drug incorporation. Leakage of thiazides from liposomes was demonstrated to be induced by dilution. Low amounts of thiazides (around 10-15%) are released when lipid concentration is over 0.1 mM, while further dilution increased drug leakage exponentially. Concluding, results demonstrate that the presence of HCT or CT in liposome membranes has a significant effect on main vesicle properties, which are known to influence vesicle targeting ability. Thereby, it is very interesting to continue studies in this respect, especially with more lipophilic drugs.

Antihypertensive Agents↗
PubMedDate not supplied

Detergent solubilization of liver microsomal acyl-coenzyme A:1-acyl-glycerophosphocholine acyltransferase in nephrotic rat.

Hyperlipidaemia is a common feature of nephrotic syndrome and this has been thought to involve increased assembly and secretion of very low density lipoprotein (VLDL) in the liver. An important pathway for an indirect modulation of VLDL. Synthesis is the reaction catalyzed by the acyl-coenzyme A:1-acyl-glycero-phosphcholine acyl transferase. We therefore investigated the activity of this enzyme in liver microsomes isolated from puromycin amino nucleoside induced nephrotic rats. When oleoyl-CoA was employed as the acyl-donor, our results indicated that both the total and detergent soluble enzyme activities (112.2 +/- 16.7; 116.1 +/- 17.5 units, respectively) were significantly higher than the corresponding control levels of 91.1 +/- 11.1 and 75.4 +/- 20.9 units respectively. The percentage stimulation by sodium cholate were 176.5 and 192.2 for the control and nephrotic rats, respectively. In absence of sodium cholate, when oleoyl CoA was replaced by arachidonoyl-CoA as acyl-donor, the measured total enzyme activity was only significantly reduced in the control rats (71.1 +/- 8.9 Vs 91.1 +/- 11.1 Units). Oleoyl-CoA as acyl-donor gave higher values for the soluble and residual enzyme activities (90.4 13.3; 99.5 34.5 unit) than the corresponding control levels (75.9 +/- 10.0; 50.5 +/- 34.0 units) as compared to arachidonoyl-CoA. In the control group the difference was only significant in the residual activity (92.9 20.5 Vs 64.7 24.1 units). The addition of monomethylethanomine (200 mM) had little or no effect, while both reduced glutathione (10 mM) and 1,2-diacylglycerol (1 mM) caused significant reduction in measured activity. These results indicated that in nephrotic rats new phospholipid synthesis is enhanced and this could contribute to the increased VLDL assembly and secretion usually associated with nephrotic syndrome.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed2001

[Transdermal delivery of cyclosporin A solubilized in mixed micelles through mice skin].

AIM: To investigate the transdermal delivery effects of cyclosporine A solubilized in mixed micelles composed of phospholipid and different surfactants. METHODS: When applied onto the excised abdominal skin of the mice occlusively, the enhancing effects of various mixed micelles on the penetration of cyclosporin A were assessed by an in vitro permeation technique. In vivo study was carried out by topical application of sodium cholate-phospholipid mixed micelles onto the mice skin and drug blood concentration was detected. RESULTS: In vitro, mixed micelles containing different surfactants displayed distinct permeability and corresponded to the following order: sodium cholate > sodium deoxycholate > Trition X-100 > Tween-20. In vivo, peak drug concentration was detected at 5 h and after that the concentration fell down slowly. CONCLUSION: Mixed micelles were shown to be efficient carrier for the transdermal delivery of the lipophilic polypeptide when kept in solution during the application process.

Administration, Cutaneous↗
PubMed2005

[Effect of bioactive water Naftussya with different microflora content on choleresis, enteroabsorbition and diuresis in rats].

Drinking of original mineral water "Naftussya" from Truskavets spa by the healthy adult rats during 3 weeks led to increase the urinary, biliary, cholates and cholesterol extraction by 54%, 72%, 69% and 83%, respectively with no influence on the enteric water absorption. The integral activity index was 2.55 +/- 0.21. Ultrafiltration of mineral water in order to eliminate microflora did not affect significantly tested properties (2.29 +/- 0.21) while ultra-violet irradiation of water increased the integral activity index to 2.67 +/- 0.47 due to enhancement of water absorption on 48% in the small intestine and increase of diuresis on 88% as well as biliary, cholesterol and cholates extraction on 74%.

Animals↗
PubMed1998

Marked reduction in bile acid synthesis in cholesterol 7alpha-hydroxylase-deficient mice does not lead to diminished tissue cholesterol turnover or to hypercholesterolemia.

These studies used mice that were deficient in cholesterol 7alpha-hydroxylase to determine the effects of reduced bile acid synthesis on cholesterol homeostasis. In mice lacking this enzyme, bile acid synthesis was reduced from 8.3 to 3.4 micromol/day per 100 g body weight, the intestinal bile acid pool was decreased from 62.5 to 13.2 micromol/100 g bw, and the proportion of hyodeoxycholate, relative to cholate, in this pool was significantly increased. Associated with these changes, intestinal cholesterol absorption decreased from 37% to <1% while triacylglycerol absorption and animal weight gain remained essentially unaffected. The very low rate of cholesterol absorption could be corrected by feeding the mutant mice cholate, but not hyodeoxycholate. The reduction in sterol uptake across the intestine was associated with a 2-fold increase in cholesterol synthesis in the small bowel and liver and an increase in fecal neutral sterol excretion from 15.2 to 35.7 micromol/day per 100 g bw. The size of the cholesterol pools in the plasma, various organs and whole animal remained constant. Thus, under circumstances where the excretion of sterol as bile acids was markedly reduced, total cholesterol turnover actually increased from 164 to 239 mg/day per kg bw. This study demonstrates the complex interactions between bile acid and cholesterol metabolism and the dramatic effects of eliminating a single gene product; however, even though a major catabolic pathway was deleted, cholesterol balance across the animal was maintained.

Animals↗
PubMed1999

Separation of linoleic acid oxidation products by micellar electrokinetic capillary chromatography and nonaqueous capillary electrophoresis.

In this work the suitability of micellar electrokinetic capillary chromatography (MEKC) and nonaqueous capillary electrophoresis (CE) to the analysis of the primary oxidation products of linoleic acid was studied with uncoated fused-silica capillaries. The primary autoxidation products of linoleic acid are the four hydroperoxide isomers 13-hydroperoxy-cis-9, trans-11-octadecadienoic acid, 13-hydroperoxy-trans-9, trans-11-octadecadienoic acid, 9-hydroperoxy-trans-10,cis-12-octadecadienoic acid, 9-hydroperoxy-trans-10, trans-12-octadecadienoic acid. Addition of a surfactant such as sodium dodecyl sulfate (SDS) or sodium cholate (SC) into the running buffer (20-30 mM 3-(cyclohexylamino)-1-propanesulfonic acid (CAPS) or ammonium acetate, pH 9.5-11) was required to enhance the water solubility of the sample and selectivity of the separation. MEKC proved to be a promising new technique for the separation of the primary oxidation products of lipids giving results comparable to high performance liquid chromatography (HPLC). Partial separation of hydroperoxide isomers was also achieved using nonaqueous CE with methanol-acetonitrile-sodium cholate as running buffer.

Chromatography, Micellar Electrokinetic Capillary↗
PubMed1999

Analysis of spiramycin by capillary electrophoresis.

The development and validation of an analytical method for the determination of spiramycin I in the presence of its related substances by capillary electrophoresis is shown. The separation, performed in a phosphate buffer (80 mM, pH 7.5) containing 12 mM cetyltrimethylammonium bromide (CTAB) and 20 mM sodium cholate, with a 50 microm ID and 44 cm long fused-silica capillary (36 cm effective length), applying a voltage of 12 kV (l approximately 80 microA), at 25 degrees C, is achieved in 15 min. Good selectivity among spiramycin I and its related substances was obtained. The influence of the buffer pH, and of the CTAB and sodium cholate concentrations was investigated. The method robustness, examined by means of a full-fraction factorial design, shows that it can be used within the limits set for the three parameters that were investigated. The method is linear (r = 0.9992) and precise (day-to-day corrected peak area repeatability, n = 18, relative standard deviation = 1.3%). The limits of detection and quantitation are 7 pg (0.025%) and 22 pg (0.08%), respectively, relative to a 2 mg/mL solution.

Aminoglycosides↗
PubMed2002

Chiral separation of benzoporphyrin derivative mono- and diacids by laser induced fluorescence-capillary electrophoresis.

A method for the separation of benzoporphyrin derivative mono- and diacid (BPDMA, BPDDA) enantiomers by laser induced fluorescence-capillary electrophoresis (LIF-CE) has been developed. By using 300 mM borate buffer, pH 9.2, 25 mM sodium cholate and 10% acetronitrile as electrolyte, +10 kV electrokinetic sampling injection of 2 s and an applied +20 kV voltage across the ends of a 37 cm capillary (30 cm to the detector, 50 microm ID), all six BPD stereoisomers were baseline-separated within 20 min. Formation constants, free electrophoretic and complexation mobilities with borate and cholate were determined based on dynamic complexation capillary electrophoresis theory. The BPD enantiomers can be quantitatively determined in the range of 10(-2)-10(-5) mg mL(-1). The correlation coefficients (r2) of the least-squares linear regression analysis of the BPD enantiomers are in the range of 0.9914-0.9997. Their limits of detection are 2.18-3.5 x 10(-3) mg mL(-1). The relative standard deviations for the separation were 2.90-4.64% (n = 10). In comparison with high-performance liquid chromatography (HPLC), CE has better resolution and efficiency. This separation method was successfully applied to the BPD enantiomers obtained from a matrix of bovine serum and from liposomally formulated material as well as from studies with rat, dog and human microsomes.

Animals↗
PubMed1977

In vitro studies of gallstone dissolution using bile salt solutions and heparinized saline.

A controlled in vitro study of gallstone dissolution has been carried out using a model designed to simulate the in vivo situation in the bile ducts. Sodium taurocholate, sodium cholate, heparinized saline and physiological saline were infused for 10 days over 81 stones from 32 patients and changes in weight and structure were recorded. The bile salt solutions caused weight loss in 81-5 and 85-7 per cent respectively of the stones treated, but the two saline solutions caused weight gains in 74-5 and 88 per cent respectively. Fragmentation occurred in 18-5% of stones treated with sodium taurocholate, in 25% of those treated with sodium cholate and in 11-8 per cent of those treated with heparinized saline. Small stones lost a lower absolute amount of weight than large stones but this represented a greater proportion of their initial weight. These investigations confirm the advantages of a dynamic in vitro model to study gallstone dissolution. Bile salt solutions infused into the bile ducts may clear retained stones by causing reduction in stone weight or fragmentation or both, but heparinized saline appears to be unsuitable for gallstone dissolution. Larger stones may require longer periods of infusion.

Bile Acids and Salts↗
PubMed2004

Biquinolino-modified beta-cyclodextrin dimers and their metal complexes as efficient fluorescent sensors for the molecular recognition of steroids.

A series of bridged beta-cyclodextrin (beta-CyD) dimers possessing functional tethers of various lengths was synthesized in moderate yield by the treatment of 2,2'-biquinoline- 4,4'-dicarboxylic dichloride with beta-CyD or mono[6-oligo(ethylenediamino)-6-deoxy]-beta-CyDs. The products were 2,2'-biquinoline-4,4'-dicarboxy-bridged bis(6-O-beta-CyD) (8), N,N'-bis(2-aminoethyl)-2,2'-biquinoline-4,4'-dicarboxamide-bridged bis(6-amino-6-deoxy-beta-CyD) (9), and N,N'-bis(5-amino-3-azapentyl)-2,2'-biquinoline-4,4'-dicarboxamide-bridged bis(6-amino-6-deoxy-beta-CyD) (10). The reaction of 8-10 with copper perchlorate give their copper(II) complexes 11-13 in satisfactory yields of over 77 %. All the bis(beta-CyD)s 8-13 act as efficient fluorescent sensors and display remarkable fluorescence enhancement upon addition of optically inert steroids. The inclusion complexation behaviors of 8-13 when treated with the representative steroids cholate (14), deoxycholate (15), and glycocholate (16) in aqueous solution at 25 degrees C were investigated by means of UV/Vis spectroscopy, conductivity and fluorescence measurements, circular dichroism spectroscopy, and 2D NMR spectroscopy. The tether length of bis(beta-CyD) 9 allows it to adopt a cooperative host-tether-guest binding mode in which the spacer and guest are co-included in the two CyD cavities. As a result of this cooperation, 9 has a stability constant (K(s)) about 2x10(2) times higher than that of monomodified beta-CyD 4 for inclusion complexation with cholate. Metallooligo(beta-CyD)s with four beta-CyD units have enhanced binding abilities compared with monomodified beta-CyDs. These metallo compounds have binding affinities for guest steroids that are up to 50-4.1x10(3) times higher than those of CyDs 2-4. The guest-induced fluorescence enhancement of bis(CyD)s opens a new channel for the design of sensor materials. The complex stability constants of these compounds are discussed from the viewpoint of induced-fit interaction and cooperative multiple binding between host and guest.

Circular Dichroism↗
PubMedDate not supplied

Kinetics and thermodynamics of dissolution of lecithin by bile salts.

The kinetics of dissolution of dispersions of egg phosphatidylcholine (lecithin) by bile salts was studied by observing the decrease in turbidity as mixed micelles of lecithin and bile salts were formed. The rate of dissolution of lecithin corresponding to formation of mixed micelles was studied in the presence of dihydroxy bile salts, sodium deoxycholate, sodium chenodeoxycholate, sodium ursodeoxycholate and one trihydroxy bile salt, sodium cholate. The rate of dissolution of lecithin and mixed micelle formation decreased in the order: chenodeoxycholate greater than deoxycholate greater than cholate greater than ursodeoxycholate. Kinetic solvent isotope studies in D2O, along with measurement of enthalpies of mixed micelle formation both in H2O and D2O, suggest that formation and stabilization of mixed micelles are related to "hydrophobicity" as estimated by high performance liquid chromatography retention factors.

Bile Acids and Salts↗