Location of probucol in lipoproteins inferred from compositional analysis of lipoprotein particles. An in-vitro study

The location of labelled probucol in lipoprotein particles was investigated in-vitro. Human serum was incubated for 4 h at 37 degrees C with [14C]probucol to incorporate probucol into lipoproteins. Serum lipoprotein particles were then isolated according to their apolipoprotein markers by sequential immunoaffinity chromatography at 4 degrees C, and probucol concentration was determined in each lipoprotein fraction. Analysis of probucol distribution vs lipoprotein components revealed that probucol in particles strongly correlated with phospholipid concentration. Analysis of probucol distribution vs lipoprotein physical characteristics showed that probucol strongly correlated with the surface area of the monolayer surrounding the lipidic core of particles constituting phospholipids and free cholesterol. These data support the hypothesis that probucol is preferentially located in the phospholipid/free cholesterol monolayer surrounding the lipid core, in the vicinity of cholesteryl ester at the core surface or in the vicinity of hydrophobic areas of apolipoprotein that faces the monolayer.