Characteristics of conjugate bile salt-phosphatidylcholine-cholesterol-water systems

Solubilization of L-alpha-phosphatidylcholine (PC) to micelles of conjugate bile salts, sodium glycocholate (NaGC), sodium taurocholates (NaTC), and sodium glycodeoxycholate (NaGDC), was studied at different bile salt concentrations by enzymatic method and by transmittance of the suspension system at 308.2 K. The solubility of PC increased in the order of NaTC < NaGC < NaGDC. An average molar ratio of PC/NaTC decreased with increasing bile salt concentration at different temperatures. Hydrodynamic diameters (d(h)) of PC-saturated conjugate bile salt aggregates were measured by dynamic light scattering (DLS or QELS) as a function of the bile salt concentration at 308.2 K. Change of the d(h) values with increasing bile salt concentration indicated shape transition from vesicle (d(h): 150 nm) to micelle (d(h): 10 nm). The maximum additive concentrations of cholesterol into the aqueous micellar solutions of PC-conjugate bile salt mixtures were spectrophotometrically determined using enzymatic analysis. The cholesterol solubility increased in the order of NaTC < NaGC at the same concentration, and in addition, cholesterol can be more solubilized at higher molar ratio of PC/bile salt. An addition of cholesterol to the PC-bile salt systems was found to become a trigger that gave rise to generation of polydisperse distribution of larger aggregates or vesicle formation for PC-bile salt systems. The critical cholesterol concentration of vesicle formation was 1.2 mM for NaTC (47.5 mM)-PC (36.5 mM) system and 0.7 mM for NaTC (47.5 mM)-PC (23.8 mM) system. (C) 2003 Elsevier B.V. All rights reserved.