The use of monolayers for simple and quantitative analysis of lipid-drug interactions exemplified with dibucaine and substance P

Abstract

The interaction between lipids and water soluble amphiphiles was investigated by means of a monolayer technique, monitoring the area increase at constant surface pressure. The area increase could be quantitated and binding isotherms at different surface pressures were measured. A comparison of dibucaine binding to monolayers and bilayers showed that a surface pressure of 32 mN/m best represents the packing density in a lipid bilayer ( Seelig, 1987). Binding isotherms measured for charged dibucaine and substance P (SP) were analyzed by means of two different models. If electrostatic effects were ignored the binding of dibucaine and SP showed biphasic Scatchard plots. If, however, electrostatic effects were taken into account by means of the Gouy-Chapman theory, the insertion of both amphiphiles was best described in terms of a partitioning into the monolayer lipids. The hydrophobic binding constant was K P = 660 ± 80 M −1 for charged dibucaine inserting into coarse liposomes or monolayers at 32 mN/m ( Seelig et al., 1986 ) and 1–1.8 M −1 for SP inserting into monolayers at 32 mN/m ( Seelig and Macdonald, 1989).