Silicone polymer uptake method for determination of cholesterol thermodynamic activity in model bile systems.
Cholesterol in bile has been linked to the incidence of gallstone disease through the concept of supersaturation as measured by the cholesterol saturation index (CSI). The latter is a linear function of cholesterol concentration and is based on the assumption that all cholesterol in bile is solubilized and transported in bile salt-lecithin (BS-L) mixed micelles, as well as in bile salt simple micelles. In light of the discovery of the cholesterol-lecithin vesicles as significant cholesterol carriers, there is a need to re-evaluate this old concept. This study examined the feasibility of the silicone polymer uptake method for the direct determination of the cholesterol thermodynamic activity (AT) in model bile systems. In cases of unsaturation and near saturation, a linear relationship was observed between CSP,Eq, the cholesterol concentration in the silicone polymer at equilibrium, and CAq,Eq/Cs,Aq for taurocholate (TC), taurochenodeoxycholate (TCDC), and tauroursodeoxycholate (TUDC) systems either containing or not containing lecithin. Here, CAq,Eq is the cholesterol concentration in the aqueous micellar solution at equilibrium, and Cs,Aq is the cholesterol monohydrate solubility of the same medium. In TC-L solutions supersaturated with cholesterol, the linear relationship continued to hold up to the point where vesicles started to form. Vesicle formation initiated a negative deviation from linearity. At constant lecithin concentration, the CSP,Eq value, or the cholesterol thermodynamic activity at which vesicle formation began, was a function of the TC:L ratio; the larger the TC:L ratio, the higher the cholesterol thermodynamic activity for the onset of vesicle formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
P H
PH
Department of Pharmaceutics, University of Utah, Salt Lake City 84112.
Cheng
D C
DC
Takayama
K
K
Higuchi
W I
WI
D001646:Bile / Q000032:analysis*; D002784:Cholesterol / Q000032:analysis*; D008055:Lipids / Q000032:analysis; D008823:Micelles; D008954:Models, Biological; D012828:Silicones; D012995:Solubility; D013816:Thermodynamics
D008055:Lipids; D008823:Micelles; D012828:Silicones; D002784:Cholesterol