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 (T m), 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.

Solubilization of negatively charged DPPC/DPPG liposomes by bile salts

“…Results by Zita [37] with NaDC/DPPC mixtures and by TomoaiaCotisel and Levin [38] with ursodeoxycholate/DPPC mixtures are in accordance with our results. Increasing the NaC amount (6 mM) induces the appearance of two peaks.…”

Phase Behavior and Nanoscale Structure of Phospholipid Membranes Incorporated with Acylated C14-Peptides

“…The pretransition is most pronounced in DSC scans of multilamellar liposomes, but has also been reported in unilamellar liposomes. Several studies have demonstrated that the occurrence of the pretransition is sensitive to the addition of various molecular compounds, such as cholesterol, gramicidin S, ursodeoxycholic, and alphaxalone (22)(23)(24)(25). Between the pre-and the main phase transitions, the lipid bilayers are characterized by regular corrugations with a periodic spatial distribution referred to as the ripple phase (26)(27)(28).…”

A Model for the Lipid Pretransition: Coupling of Ripple Formation with the Chain-Melting Transition

“…Cholesterol affects the ripple periodicity and lowers the pretransition temperature in DMPC (Mortensen et al, 1988;Matuoka et al, 1994). The pretransition is abolished upon the addition of gramicidin S (Prenner et al, 1999), cannabinoids (Mavromoustakos, 1996), sphingosine (Koiv et al, 1993), ursodeoxycholate (Tomoaia-Cotisel and Levin, 1997), various anesthetics (Engelke et al, 1997), and ceramides (Holopainen et al, 1997). There are indications that the absence of the pretransition in DPPC-membranes containing anesthetic steroids may be the consequence of an extreme broadening such that it is not evident in heat capacity (c p )-traces but is visible by other means (Mavromoustakos et al, 1997).…”