Partitioning of a homologous series of alkyl p-aminobenzoates in dipalmitoylphosphatidylcholine liposomes: effect of liposome type

The partitioning of a homologous series of n-alkyl p-aminobenzoates into the lipid bilayer is dependent not only on their physicochemical properties but also on liposome type. Partitioning studies with this homologous series demonstrate the effect of alkyl chain length on partitioning in DPPC multilamellar liposomes (MLV) and DPPC MLV extruded through 1 or 0.4 pm polycarbonate filters. A general trend was observed wherein increasing alkyl chain length increased partitioning of drug into the bilayer. The distribution coefficients of the esters were found to be strongly influenced by the physical structure of the membrane. Factors which decrease the surface density of the bilayer, such as temperature. will also increase solute partitioning into the bilayer. The amounts of the alkyl p-aminobenzoates included in the bilayers of DPPC multilamellar liposomes at 23 o C were quite low because the high surface density of the bilayer at 23 ‘C precludes the incorporation of solute. The extruded liposomes studied were much smaller and are believed to have greater bilayer fluidity and disorder than their MLV counterparts, thus allowing greater incorporation of the alkyl p-aminobenzoates in the extruded DPPC bilayer. Hence, higher distribution coefficients and lower free energies of partitioning are achieved with extruded liposomes. The effect of extrusion on solute partitioning was found to be similar to the effects caused by increasing temperature.