Bile salts form mixed micellar solutions with lecithin. These mixed micelles solubilize lipids including cholesterol. Gallstone disease is attributed to the failure of bile to keep cholesterol in solution. Therefore an understanding of the factors which determine cholesterol solubility in bile is important in the management and prevention of gallstone disease. It is the objective of this project to characterize these solutions by determining their thermodynamic properties. Calorimetric measurements will be performed to measure the heats of interaction of bile salts with lecithin, and the heats of solution of cholesterol in these mixed micellar solutions. In addition, heat capacities, volumes and osmotic and activity coefficients will be obtained. These data will be interpreted to determine the nature of the interactions between the various components in solution. Special attention will be paid to chenodexoycholic acid and ursodeoxycholic acid and their conjugates since these substances have been effective in the treatment of gallstone disease. It is expected that a better understanding of the factors which determine lipid solubility will aid in the choice of conditions to enhance dissolution of cholesterol and thereby provide a rational basis for improved therapy and prophylaxis.
NIH ExPorter
NIH ExPorter