Interaction of dipyridamole with lipids in mixed Langmuir monolayers

Dipyridamole (DIP), a well known coronary vasodilator and coactivator of anti-tumor activity of a number of drugs, forms stable Langmuir monolayers with the zwitterionic lipid dipalmitoylphosphatidylcholine (DPPC) and the negatively charged dipalmitoylphosphatidylglycerol (DPPG) at an air/aqueous solution interface. The drug binds to the lipid molecules and change their packing density in the monolayer in the process of compression, the effect depending on the drug location in the monolayer, protonation of the drug and also on the charge state of the lipid. The incorporation of dipyridamole (DIP) into neutral DPPC monolayers causes them to be more expanded at low DIP concentrations but more condensed at high concentrations, resembling the effect of cholesterol. Maximum expansion occurs for a DIP concentration of 2 mol%. For slightly charged DPPG monolayers spread on ultra pure water, the monolayers become increasingly more expanded with increasing DIP concentrations. For the negatively charged DPPG monolayers spread on buffer solutions, the incorporation of DIP has similar effects to that observed for DPPC monolayers. This is probably due to the interaction between the charged DPPG molecules and the protonated DIP molecules. Also, introduction of protonated DIP brings an increase in surface potential of DPPG monolayers because the negative contribution from the double layer is decreased. The results indicated that DIP molecules are located deeper in the hydrophobic region of DPPC monolayers, whereas in DPPG ones they appear to be located very close to the polar head region. Due to the electrostatic interaction of protonated DIP with the charges on the polar heads of lipids it is inclined with respect to the plane of the monolayer.