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 (β) in the studied binary mixed micelles had negative value, suggesting synergism between micelle building units. Based on β 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 β 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.

The plot of specific conductivity (κ) of sodium salts of cholic acid + 7,12-dioxoL mixtures vs. total concentration at some mole fractions (I: 0.01; II: 0.02; III: 0.04; IV: 0.08). The scale shown is for I: 0.01. Other curves have been shifted upwards by 1, 2, 3 scale units..Figure optionsDownload as PowerPoint slideHighlights
► The great synergistic effect in mixed micelles arises as a result of hydrogen bonds.
► The partition coefficient (Kp) of nitrazepam is greater in mixed micelles with hydrophobic bile acids.
► The increase in the number of hydrogen bonds reduces Kp values of nitrazepam.