Moxifloxacin interacts with lipid bilayer, causing dramatic changes in its structure and phase transitions

• Published in: Chemistry and physics of lipids 2020-05, Vol.228, p.104891-104891, Article 104891
• Main Authors: Le-Deygen, Irina M., Skuredina, Anna A., Safronova, Anastasia S., Yakimov, Ivan D., Kolmogorov, Ilya M., Deygen, Daria M., Burova, Tatiana V., Grinberg, Natalia V., Grinberg, Valery Y., Kudryashova, Elena V.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Biochemical analysis; Calorimetry, Differential Scanning; Circular Dichroism; DSC; Fluorescence; Fluoroquinolones; FTIR; Lipid Bilayers - chemistry; Liposomes; Molecular Structure; Moxifloxacin; Moxifloxacin - pharmacology; Phase Transition; Spectrophotometry, Ultraviolet; Spectroscopy; Spectroscopy, Fourier Transform Infrared
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2020.104891

[Display omitted] •Moxifloxacin interacts with lipid bilayer, causing changes in its structure and phase transitions especially for anionic liposomes.•For the first time, the fine structure of bilayer complexes with moxifloxacin in all details was determined.•Combined spectral approach to study drug-to-lipid interaction and analyze fine structure of complexes is developed.•Cardiolipin in lipid matrix composition provides stronger binding of moxifloxacin.•Mox interacts with two microphases of DPPC/CL liposomes esulting formation of two types of the complexes. Most drugs besides their intended activity, express undesired side effects, including those with the engagement of cell membrane. Previously, such undesired nonspecific effects on the membrane have been shown for a number of widely used nonsteroidal anti-inflammatory drugs. In this paper, we study the mechanism of interaction between moxifloxacin (Mox), antibacterial drug of broad specificity, with lipid bilayer of the liposomes of various compositions as a model of cell membrane using a combination of spectroscopy methods, including ATR-FTIR spectroscopy, circular dichroism, UV and fluorescence spectroscopy. The fine structure of the moxifloxacin-liposome complex, localization of the drug in bilayer and the main sites of Mox interaction with lipid membrane were determined. Lipid composition of the liposome plays a key role in the interaction with moxifloxacin, drastically affecting the loading efficiency, strength and character of drug binding, lipid phase segregation and phase transition parameters. In case of anionic liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and cardiolipin (CL2−) the electrostatic interaction of negatively charged nitrogen in heterocycle moiety of moxifloxacin with cardiolipin phosphate groups is a crucial factor for stable complex formation. The study of moxifloxacin-liposome complex behavior at phase transition in bilayer by DSC method revealed that in DPPC/CL2− liposomes system two microphases with different content of CL2- coexist and Mox interacts with both of these microphases resulting in the formation of two types of complexes with different structure and phase transition temperature. This binding stabilized the gel-state of the lipid bilayer with increasing the phase transition temperature Tm up to 3−5 °C. A different situation is observed for neutral DPPC liposomes: drug interaction with bilayer results in defects formation and a fluidization effect in l