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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.

— We have studied the interaction of the antibacterial drug levofloxacin with lipid bilayers of various compositions: 100% DPPC and with the addition of 20% cardiolipin. For DPPC liposomes, levofloxacin was found to penetrate into the subpolar region at the lipid–water interface. The role of the anionic lipid in the interaction of an active molecule with a bilayer has been established: levofloxacin enters the microenvironment of the phosphate group, displacing water, and does not penetrate into the hydrophobic part of the bilayer. For the first time, the study of the microenvironment of levofloxacin in the liposome by IR and CD spectroscopy was carried out. Such an approach based on a combination of several spectral methods opens up new prospects for the creation of new medicinal properties and the possibility of predicting the nature of the interaction of active molecules with biomembranes in order to predict their efficacy and potential side effects.

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