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

Irina M Le-Deygen; Anna A Skuredina; Anastasia S Safronova; Ivan D Yakimov; Ilya M Kolmogorov; Daria M Deygen; Tatiana V Burova; Natalia V Grinberg; Valery Y Grinberg; Elena V Kudryashova

doi:10.1016/j.chemphyslip.2020.104891

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

Chem Phys Lipids. 2020 May:228:104891. doi: 10.1016/j.chemphyslip.2020.104891. Epub 2020 Feb 10.

Affiliations

¹ Lomonosov MSU, Faculty of Chemistry, Chemical Enzymology Department, 119991, Moscow, Leninskie Gory, 1, 3, Russia. Electronic address: i.m.deygen@gmail.com.
² Lomonosov MSU, Faculty of Chemistry, Chemical Enzymology Department, 119991, Moscow, Leninskie Gory, 1, 3, Russia.
³ A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences (INEOS RAS), 119991, Moscow, Vavilova St. 28, Russia.

PMID: 32057752
DOI: 10.1016/j.chemphyslip.2020.104891

Abstract

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 (CL^2-) 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/CL^2- liposomes system two microphases with different content of CL^2- 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 lipid bilayer, resulted to decrease the Tm value by 2-4 °C. Moxifloxacin is not firmly binding in the membrane of DPPC and drug releases rapidly.

Keywords: Biochemical analysis; DSC; FTIR; Fluorescence; Fluoroquinolones; Liposomes; Moxifloxacin; Spectroscopy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology*
Calorimetry, Differential Scanning
Circular Dichroism
Lipid Bilayers / chemistry*
Molecular Structure
Moxifloxacin / pharmacology*
Phase Transition
Spectrophotometry, Ultraviolet
Spectroscopy, Fourier Transform Infrared

Substances

Anti-Bacterial Agents
Lipid Bilayers
Moxifloxacin