Journal of Lipid Research (Sep 1971)
Micellar properties of sodium fusidate, a steroid antibiotic structurally resembling the bile salts
Abstract
The properties of sodium fusidate micelles were determined by a spectral shift technique, surface tension measurements, and ultracentrifugal analysis. The critical micellar concentrations, mean molecular areas, and apparent aggregation numbers were estimated as a function of the concentration of counterion (0.001–1.0 m Na+) at 20°C. The critical micellar concentrations were studied over a temperature range of 10°C to 40°C at one counterion concentration (0.001 m Na+), and from these data the standard thermo-dynamic functions of micellization were calculated. The ability of sodium fusidate solutions to solubilize the insoluble swelling amphiphiles, lecithin and monoolein, was investigated, and the results were compared with the solubilizing properties of sodium taurocholate.The critical micellar concentrations of sodium fusidate approximated those of sodium taurocholate. The values fell in the range of 1.44–4.56 mm, varying with the technique used, counterion concentration, and temperature. The percentage of counterions bound to fusidate micelles in water, calculated from the log critical micellar concentration–log Na+ curve, was estimated to be negligible, which compares with sodium taurocholate micelles. The critical micellar concentration of sodium fusidate exhibited a minimum at 20°C, a phenomenon observed with other ionic detergents and with bile salts. Micelle formation in sodium fusidate solutions was shown to be primarily entropy-driven at 10° and 20°C, whereas at 30° and 40°C the enthalpy factor predominated. From the surface tension measurements the molecular areas of sodium fusidate and sodium taurocholate were calculated. The mean molecular area of fusidate was 101 A2, whereas sodium taurocholate possessed a molecular area of 88 A2. It was demonstrated that the sodium fusidate molecule, like a bile salt molecule, lies with its longitudinal axis horizontal at an air–water interface. The apparent aggregation number of sodium fusidate micelles increased from 5 to 16 as the concentration of counterion increased from 0.01 to 0.60 m Na+. These values are slightly larger than the corresponding aggregation numbers of sodium taurocholate micelles.Sodium fusidate is thus similar to the bile salt sodium taurocholate in its micellar properties. Furthermore, saturation ratios similar to those found with bile salt solutions were obtained when liquid crystalline suspensions of lecithin or monoglyceride were solubilized by sodium fusidate solutions. As excretion of orally administered fusidate occurs mainly via the biliary tract, this finding may prove to be of considerable biological importance. A model of the fusidate micelle similar to that previously proposed for the bile salt micelle is suggested.
