Drug–Membrane Interaction as Revealed by Spectroscopic Methods: The Role of Drug Structure in the Example of Rifampicin, Levofloxacin and Rapamycin

Abstract

We have investigated the nature of the interaction of small organic drug molecules with lipid membranes of various compositions. Using infrared spectroscopy and differential scanning calorimetry methods, we studied the role of the structure of the active molecule in interaction with the membrane using the example of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylcholine:cardiolipin (DPPC:CL) liposomes. We discovered the key role of the heterocycle in interaction with the polar part of the bilayer and the network of unsaturated bonds in interaction with the hydrophobic part. For rifampicin and levofloxacin, the main binding sites were phosphate and carbonyl groups of lipids, and in the case of anionic liposomes we found a slight penetration of rifampicin into the hydrophobic part of the bilayer. For rapamycin, experimental confirmation of the localization of the molecule in the region of fatty acid chains was obtained, and perturbation in the region of phosphate groups was demonstrated for the first time. The process of phase transition of liposomal forms of rifampicin and levofloxacin was studied. DPPC liposomes accelerate the phase transition when loaded with a drug. DPPC:CL liposomes are less susceptible to changes in the phase transition rate.