Partitioning of an homologous series of alkyl p-aminobenzoates into multilamellar liposomes: effect of liposome composition

Abstract

The partitioning of the n-alkyl-p-aminobenzoates into the lipid bilayer is dependent not only on their physicochemical properties, but also on temperature and bilayer composition. Partitioning studies with this homologous series demonstrate the effect of alkyl chain length on partitioning in pure DPPC liposomes at 23 and 50 [deg]C and in DPPC: Chol liposomes at 23 [deg]C. A general trend is observed wherein increasing alkyl chain length increases partitioning of the drug into the bilayer. It is also shown that inclusion of cholesterol in the bilayer or increasing the temperature increases the partitioning of the n-alkyl p-aminobenzoates into the bilayer. The distribution coefficients are strongly influenced by the physical structure/state of the membrane. Therefore, factors which increase the fluidity of the bilayer will also increase solute partitioning into the bilayer. Compounds that are highly lipid soluble, such as butyl p-aminobenzoate, will preferentially partition into the bilayer, and are relatively insensitive to bilayer composition or to structural changes within the bilayer.