Thermodynamic Study of the Effects of Ursodeoxycholic Acid and Ursodeoxycholate on Aqueous Dipalmitoyl Phosphatidylcholine Bilayer Dispersions

Abstract

The effects of ursodeoxycholic acid (UDCAH) and ursodeoxycholate (UDCA-) on the thermotropic phase behavior of aqueous bilayer dispersions of 1,2-dipalmitoyl-3-sn-phosphatidylcholine (DPPC), buffered at pH 7.0, were examined by differential scanning calorimetry (DSC) for concentrations of UDCAH and UDCA- (represented by UDCA) from 0 to approximately 76 mol %. The calorimetric data show that progressively increasing UDCA concentrations decreases the DPPC bilayer main transition temperatures (Tm), while increasing the widths of the gel to liquid crystalline phase transition endotherms. The DPPC bilayer pretransition is suppressed in the presence of UDCA at the lowest concentrations employed. The calorimetric data, which are interpreted in terms of the partition equilibria of UDCAH and UDCA- and of the DPPC bilayer phase transition enthalpies and Gibbs free energies, allow the development of a thermodynamic approach for determining the phase boundaries in mixed DPPC:UDCA dispersions. In particular, for concentrations of UDCA up to approximately 25 mol %, the gel to liquid crystalline phase transition enthalpies of the mixed DPPC:UDCA bilayers remain essentially constant. The increase that occurs in the DPPC gel to liquid crystalline phase transition enthalpies for UDCA concentrations between approximately 25−60 mol % is interpreted in terms of an induced interdigitated gel (LgI) phase stabilized by specific DPPC:UDCA molecular interactions. The data suggest that the interdigitated gel phase exists in equilibrium with micelles, whose structures remain to be elucidated, of various UDCA:DPPC mole ratios. Finally, concentrations of UDCA in amounts greater than 60 mol % result in constant DPPC phase transition temperatures and enthalpies.