Selective solubilization of sterols by bile salt micelles in water: A thermodynamic study

To study thermodynamically the so-called lowering effect of the plasma cholesterol level caused by dietary intake of phytosterols (plant sterols) or phytostanols, solubilization was investigated for the respective single systems of cholesterol (Ch), cholestanol (Chsta), and stigmasterol (Stig) and for their 1:1 mixed systems with two kinds of free bile salts (BS), sodium cholate (NaC) and sodium deoxycholate (NaDC), in pH 10 Kolthoff buffer solution at 37 degreesC. For the sterol/stanol solubilizates examined, compared with NaC, NaDC is stronger in solubilizing power, Sp, which is defined as the derivative of the solubilized amount, W, in mM by the total BS concentration, C-t (dW/dC(t)), as expected in terms of hydrophobicity and aggregation number. The following findings were made: (i) the amount solubilized by both BS micelles follows the order Ch > Chsta > Stig among the three single solubilizates; (ii) Chsta is much stronger in lowering ability than Stig in regard to Ch solubilization; (iii) from the 1:1 mixture of Ch with Chsta, Chsta is selectively solubilized (Ch is selectively excluded) by BS micelles. A thermodynamics analysis allowed us to conclude that Sp could be related to the standard Gibbs energy change of translation from crystalline to solubilized states as Delta Gs(theta) = -RT ln S-p for single solubilizate systems and Delta Gs(theta (mix)) = -RT ln S-p(mix) for mixed solubilizate systems. Further, based on the regular solution theory, the miscibility of two solubilizates, A and B, inside micelles was evaluated in terms of the excess Gibbs energy change (enthalpy term) of mixing Delta Gs((ex)), activity coefficients gamma (i) (i = A, B), and interaction parameter omega. The omega values and Delta Gs((ex)) values are negative for Stig/Ch, while they are positive for Chsta/Ch, reflecting the highly selective solubilization.