Characterization of the interactions between fluoroquinolone antibiotics and lipids: a multitechnique approach.
Probing drug/lipid interactions at the molecular level represents an important challenge in pharmaceutical research and membrane biophysics. Previous studies showed differences in accumulation and intracellular activity between two fluoroquinolones, ciprofloxacin and moxifloxacin, that may actually result from their differential susceptibility to efflux by the ciprofloxacin transporter. In view of the critical role of lipids for the drug cellular uptake and differences observed for the two closely related fluoroquinolones, we investigated the interactions of these two antibiotics with lipids, using an array of complementary techniques. Moxifloxacin induced, to a greater extent than ciprofloxacin, an erosion of the DPPC domains in the DOPC fluid phase (atomic force microscopy) and a shift of the surface pressure-area isotherms of DOPC/DPPC/fluoroquinolone monolayer toward lower area per molecule (Langmuir studies). These effects are related to a lower propensity of moxifloxacin to be released from lipid to aqueous phase (determined by phase transfer studies and conformational analysis) and a marked decrease of all-trans conformation of acyl-lipid chains of DPPC (determined by ATR-FTIR) without increase of lipid disorder and change in the tilt between the normal and the germanium surface (also determined by ATR-FTIR). All together, differences of ciprofloxacin as compared to moxifloxacin in their interactions with lipids could explain differences in their cellular accumulation and susceptibility to efflux transporters.
Bensikaddour
Hayet
H
Université Catholique de Louvain, Faculty of Medicine, Unité de Pharmacologie Cellulaire et Moléculaire, Brussels, Belgium.
Fa
Nathalie
N
Burton
Ingrid
I
Deleu
Magali
M
Lins
Laurence
L
Schanck
André
A
Brasseur
Robert
R
Dufrêne
Yves F
YF
Goormaghtigh
Erik
E
Mingeot-Leclercq
Marie-Paule
MP
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001372:Aza Compounds / Q000737:chemistry*; D002939:Ciprofloxacin / Q000737:chemistry*; D045424:Complex Mixtures / Q000737:chemistry; D024841:Fluoroquinolones / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry*; D021962:Membrane Microdomains / Q000737:chemistry*; D018625:Microscopy, Atomic Force / Q000379:methods; D008968:Molecular Conformation; D000077266:Moxifloxacin; D044367:Phase Transition; D010743:Phospholipids / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013499:Surface Properties
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D045424:Complex Mixtures; D024841:Fluoroquinolones; D008563:Membrane Lipids; D010743:Phospholipids; D011804:Quinolines; D002939:Ciprofloxacin; D000077266:Moxifloxacin