Interactions of ciprofloxacin with DPPC and DPPG: Fluorescence anisotropy, ATR-FTIR and 31P NMR spectroscopies and conformational analysis

Abstract

The interactions between a drug and lipids may be critical for the pharmacological activity. We previously showed that the ability of a fluoroquinolone antibiotic, ciprofloxacin, to induce disorder and modify the orientation of the acyl chains is related to its propensity to be expelled from a monolayer upon compression [1]. Here, we compared the binding of ciprofloxacin on DPPC and DPPG liposomes (or mixtures of phospholipids [DOPC:DPPC], and [DOPC:DPPG]) using quasi-elastic light scattering and steady-state fluorescence anisotropy. We also investigated ciprofloxacin effects on the transition temperature (T(m)) of lipids and on the mobility of phosphate head groups using Attenuated Total Reflection Fourier Transform Infrared-Red Spectroscopy (ATR-FTIR) and (31)P Nuclear Magnetic Resonance (NMR) respectively. In the presence of ciprofloxacin we observed a dose-dependent increase of the size of the DPPG liposomes whereas no effect was evidenced for DPPC liposomes. The binding constants K(app) were in the order of 10(5) M(-1) and the affinity appeared dependent on the negative charge of liposomes: DPPG>DOPC:DPPG (1:1; M:M)>DPPC>DOPC:DPPC (1:1; M:M). As compared to the control samples, the chemical shift anisotropy (Deltasigma) values determined by (31)P NMR showed an increase of 5 and 9 ppm for DPPC:CIP (1:1; M:M) and DPPG:CIP (1:1; M:M) respectively. ATR-FTIR experiments showed that ciprofloxacin had no effect on the T(m) of DPPC but increased the order of the acyl chains both below and above this temperature. In contrast, with DPPG, ciprofloxacin induced a marked broadening effect on the transition with a decrease of the acyl chain order below its T(m) and an increase above this temperature. Altogether with the results from the conformational analysis, these data demonstrated that the interactions of ciprofloxacin with lipids depend markedly on the nature of their phosphate head groups and that ciprofloxacin interacts preferentially with anionic lipid compounds, like phosphatidylglycerol, present at a high content in these membranes.

Influence of Lipid Composition, pH, and Temperature on Physicochemical Properties of Liposomes with Curcumin as Model Drug

“…Fluorescence anisotropy is directly related to the microviscosity of a medium 11,59 . Variations in the fluorescence anisotropy r of curcumin, loaded in liposomes, with pH are shown in panel C of Fig.…”

“…Numerous studies in the field of lipo-DPPC with both the acyl chains is saturated and thus solid up to 41 10 . Dipalmitoylphosphatidylglycerol DPPG is negatively charged because of its uncharged glycerol head group 11 . A DPPC-DPPG mixture is the major component of lung surfactant and necessary for the formation of lipidprotein conjugates, such as tubular myelin located in alveoli in the lungs 12 .…”

Interaction of oligonucleotide-based amphiphilic block copolymers with cell membrane models

“…However, when mixed to the nucleotide-based copolymers, DPPC could be transferred as multilayers up to 11 layers. The bands centered at 1376, 1741, 2842 and 2921 cm À1 are assigned respectively to the scissoring mode of CH 2 attached to PO, stretching of carbonyl group, and symmetric and asymmetric modes of CH 2 , in agreement with data for DPPC in the literature [30]. The main bands for the nucleotide-based copolymer also are observed at 966 cm À1 (CH out-of-plane deformation), 1105 cm À1 (CAOAC from the nitrogen base), 1641 cm À1 (C@C from PB, or C@O from the nitrogen base), 2840 and 2912 cm À1 (CH 2 stretches).…”

Laser interferometry analysis of ciprofloxacin and ampicillin diffusion from liposomal solutions to water phase

“…1996; Bensikaddour et al. 2008). In contrast to ciprofloxacin, ampicillin like β-lactam does not change the internal osmotic pressure or the optical density of liposomes.…”