M. Tomoaiacotisel et Iw. Levin, THERMODYNAMIC STUDY OF THE EFFECTS OF URSODEOXYCHOLIC ACID AND URSODEOXYCHOLATE ON AQUEOUS DIPALMITOYL PHOSPHATIDYLCHOLINE BILAYER DISPERSIONS, JOURNAL OF PHYSICAL CHEMISTRY B, 101(42), 1997, pp. 8477-8485
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 concen
trations of UDCAH and UDCA(-) (represented by UDCA) from 0 to approxim
ately 76 mol %. The calorimetric data show that progressively increasi
ng UDCA concentrations decreases the DPPC bilayer main transition temp
eratures (T-m), while increasing the widths of the gel to liquid cryst
alline phase transition endotherms. The DPPC bilayer pretransition is
suppressed in the presence of UDCA at the Lowest concentrations employ
ed. The calorimetric data, which are interpreted in terms of the parti
tion equilibria of UDCAH and UDCA(-) and of the DPPC bilayer phase tra
nsition 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 transitio
n enthalpies of the mixed DPPC:UDCA bilayers remain essentially consta
nt. The increase that occurs in the DPPC gel to liquid crystalline pha
se transition enthalpies for UDCA concentrations between approximately
25-60 mol % is interpreted in terms of an induced interdigitated gel
(L-gI) phase stabilized by specific DPPC:UDCA molecular interactions.
The data suggest that the interdigitated gel phase exists in equilibri
um with micelles, whose structures remain to be elucidated, of various
UDCA:DPPC mole ratios. Finally, concentrations of UDCA in amounts gre
ater than 60 mol % result in constant DPPC phase transition temperatur
es and enthalpies.