Estimation of cholesterol solubilization by a mixed micelle binding model in aqueous tauroursodeoxycholate:lecithin:cholesterol solutions.
In order to interpret the clinical efficacy of conjugated ursodeoxycholate (UDC) in cholesterol (Ch) gallstone patients, the Ch solubilization in mixed micelles in 40:40:32 mM tauroursodeoxycholate (TUDC):taurochenodeoxycholate (TCDC):lecithin (L) and 80:32 mM TUDC:L systems was estimated by using a model of Ch binding to mixed micelles. The Ch solubilization limit in mixed TUDC:L micelles was found to be higher than that in mixed TUDC:TCDC:L micelles. In the 80:32 mM TUDC:L system, the dissolution of the Ch pellet decreased after vesicles (liposomes) formed on the surface of the Ch pellet whereas the dissolution of microcrystalline Ch was rapid before and after vesicle formation in the solution, indicating that the total surface area of solid Ch exposed to the solution may be another important factor in inducing the dissolution of Ch gallstones. These phenomena suggest that although vesicles, occasionally formed in the bile of patients under the therapy of conjugated UDC, make a contribution to the solubilization of Ch gallstones, the model of Ch binding to mixed TUDC:L micelles can be used to estimate Ch solubility in TUDC:L system.
Higuchi
William I
WI
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Tzeng
Chinn-Shin
CS
Chang
Shyh-Jye
SJ
Chiang
Huey-Jenn
HJ
Liu
Chen-Lun
CL
D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D054709:Lecithins / Q000737:chemistry*; D008027:Light; D008081:Liposomes; D008823:Micelles; D008956:Models, Chemical; D015233:Models, Statistical; D012542:Scattering, Radiation; D012995:Solubility; D012996:Solutions; D013655:Taurochenodeoxycholic Acid / Q000737:chemistry*