Ternary Mixed Micelle Hexadecyltrimethylammonium Bromide-Dodecyltrimethylammonium Bromide-Sodium Deoxycholate: Gibbs Free Energy of Mixing and Excess Gibbs Energy of Mixing.

Pharmaceutical, food, and cosmetic formulations often contain binary or ternary surfactant mixtures with synergistic interactions amongst micellar building blocks. Here, a ternary mixture of the surfactants hexadecyltrimethylammonium bromide, dodecyltrimethylammonium bromide, and sodium deoxycholate is examined to see if the molar fractions of the surfactants in the ternary mixed micellar pseudophase are determined by the interaction coefficients between various pairs of the surfactants or by their propensity to self-associate. Critical micelle concentrations (CMC) of the analyzed ternary mixtures are determined experimentally (spectrofluorimetrically using pyrene as the probe molecule). Thermodynamic parameters of ternary mixtures are calculated from CMC values using the Regular Solution protocol. The tendency for monocomponent surfactants to self-associate (lower value of CMC) determines the molar fractions of surfactant in the mixed micelle if there is no issue with the packing of the micelle building units of the ternary mixed micelle. If a more hydrophobic surfactant is incorporated into the mixed micelle, the system (an aqueous solution of surfactants) is then the most thermodynamically stabilized.

Self-association of sodium isoursodeoxycholate and sodium isohenodeoxycholate in water.

Bile salts (BS) form hydrophobic Small's primary micelles at concentrations above the critical micelle concentration (CMC), while at concentrations above 3CMC they form secondary micelles (by the association of primary micelles via H-bonds). In this paper the self-associations of the anions of isohenodeoxycholic acid (3-epimer of henodeoxycholic acid, ICD) and the anions of isoursodeoxycholic acid (3-epimer of ursodeoxycholic acid, IUD) are examined, since the thermodynamic parameters of their self-association have not yet been published. Forming of IUD aggregates with two or three building units is slightly more favorable via α sides of steroid skeletons, regarding hydrophobicity, while regarding steric repulsive interactions it is more favorable to associate via ß sides. Due to this, IUD in the vicinity of the CMC can form primary micelles by association of IUD particles both from the convex side and from the concave side of the steroid ring system. Therefore, IUD is significantly more prone to initial micellization than bile salt derivatives whose steroidal skeletons contain equatorially oriented OH groups.

Individualization of a pharmacokinetic model by fractional and nonlinear fit improvement.

This study presents application of a new linear and nonlinear fractional derivative two compartmental model to the evaluation of individual pharmacokinetics. In the model, the integer order derivatives are replaced by derivatives of real order. A specific nonlinear function is used for the fit improvement of a fractional derivative two compartmental model with the mass balance conservation. The agreement of the values predicted by the proposed model with the values obtained through experiments with bumetanide tablets in human volunteers is shown to be good. Thus, pharmacokinetics of bumetanide can be described well by a linear or a nonlinear two compartmental model with fractional derivatives of the same order proposed here. Parameters in the model are determined by the least squares method and the particle swarm optimization numerical procedure is used. The results show that the linear fractional order two compartmental model for bumetanide is useful improvement of the classical (integer order) two compartmental model and that the nonlinear fractional order model is useful improvement of the linear model in a great number of volunteers.

Mixed micelles of 7,12-dioxolithocholic acid and selected hydrophobic bile acids: interaction parameter, partition coefficient of nitrazepam and mixed micelles haemolytic potential.

The formation of mixed micelles built of 7,12-dioxolithocholic and the following hydrophobic bile acids was examined by conductometric method: cholic (C), deoxycholic (D), chenodeoxycholic (CD), 12-oxolithocholic (12-oxoL), 7-oxolithocholic (7-oxoL), ursodeoxycholic (UD) and hiodeoxycholic (HD). Interaction parameter (ß) in the studied binary mixed micelles had negative value, suggesting synergism between micelle building units. Based on ß value, the hydrophobic bile acids formed two groups: group I (C, D and CD) and group II (12-oxoL, 7-oxoL, UD and HD). Bile acids from group II had more negative ß values than bile acids from group I. Also, bile acids from group II formed intermolecular hydrogen bonds in aggregates with both smaller (2) and higher (4) aggregation numbers, according to the analysis of their stereochemical (conformational) structures and possible structures of mixed micelles built of these bile acids and 7,12-dioxolithocholic acid. Haemolytic potential and partition coefficient of nitrazepam were higher in mixed micelles built of the more hydrophobic bile acids (C, D, CD) and 7,12-dioxolithocholic acid than in micelles built only of 7,12-dioxolithocholic acid. On the other hand, these mixed micelles still had lower values of haemolytic potential than micelles built of C, D or CD. The mixed micelles that included bile acids: 12-oxoL, 7-oxoL, UD or HD did not significantly differ from the micelles of 7,12-dioxolithocholic acid, observing the values of their haemolytic potential.

Isoflavone composition, total polyphenolic content, and antioxidant activity in soybeans of different origin.

Twenty soybean cultivars, originating from the United States, Russia, Serbia, and China, were analyzed for their isoflavone composition, total polyphenolic content, and antioxidant activity. Isoflavones were extracted by aqueous methanol (80%) and analyzed by high-performance liquid chromatography/diode array detection. Precision and linearity of the applied method were within the standard limits of validation. The highest and the lowest total isoflavone contents were 4.59 and 1.45 mg/g of dried soybean weight, respectively. A significant difference (P < .05) was found in isoflavone concentration among the different cultivars, but it was observed that origin is not a significant factor that could influence isoflavone content in soybeans. Total polyphenolic content varied between 2.13 and 3.45 mg of gallic acid equivalents/g of dried soybean weight. The free radical scavenging activity of soybean extracts assayed by 2,2-diphenyl-1-picrylhydrazyl in terms of 50% inhibitory concentration (IC(50)) ranged from 1.40 to 3.35 mg/mL. Negative correlation between total polyphenolic content and IC(50) was observed, but there was no correlation between total isoflavone content and IC(50). On the basis of this study, soybean cultivars with larger potency for biological activity could be recognized.

Determination of phytoestrogen composition in soybean cultivars in Serbia.

The growing clinical interest and use of soybean-based food products and extracts to increase dietary phytoestrogen intake have led to medical interest in the precise determination of the phytoestrogen composition of soybean products. We have analyzed the composition of these compounds in 20 domestic and introduced varieties of genetically non-modified soybean genotypes grown under the same agroecological conditions. The isoflavone content of soybeans cultivated in this region of Serbia has not been previously reported. The assays were performed, after extraction with methanol-water (8:2, v/v), by C18 reversed phase high-performance liquid chromatography coupled with photodiode array detection. The total phytoestrogen concentration was found to be between 2.24 and 3.79 mg g(-1) dry bean weight. The total concentration of daidzein and its derivatives ranged from 0.96 to 1.82 mg g(-1), total glyciteines from 0.34-0.53 mg g(-1), and all genistein derivatives from 0.86-1.67 mg g(-1) dry bean weight. Given the high biological potency of phytoestrogens and their metabolic conversion products, our data suggest that phytoestrogen content screening could be a useful tool in the selection of soybean genotypes with improved health promoting characteristics.