TY - JOUR
T1 - Interactions of ciprofloxacin with DPPC and DPPG
T2 - Fluorescence anisotropy, ATR-FTIR and 31P NMR spectroscopies and conformational analysis
AU - Bensikaddour, Hayet
AU - Snoussi, Karim
AU - Lins, Laurence
AU - Van Bambeke, Françoise
AU - Tulkens, Paul M.
AU - Brasseur, Robert
AU - Goormaghtigh, Erik
AU - Mingeot-Leclercq, Marie Paule
N1 - Funding Information:
H.B. is a doctoral assistantship recipient of the Catholic University of Louvain (UCL), E.G and R.B. are Research Directors, F.V B. is Senior Research Associate and L.L. is Research Associate of the National Foundation for the Scientific Research (F.N.R.S.). The support of the Région wallonne, of the F.N.R.S., of the Université catholique de Louvain (Fonds Spéciaux de Recherche, Actions de Recherche Concertées), of the Federal Office for Scientific, Technical and Cultural Affairs (Interuniversity Poles of Attraction Programme) is gratefully acknowledged. We also thank Bayer Healthcare AG for providing us with ciprofloxacin.
PY - 2008/11
Y1 - 2008/11
N2 - 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 (Tm) of lipids and on the mobility of phosphate head groups using Attenuated Total Reflection Fourier Transform Infrared-Red Spectroscopy (ATR-FTIR) and 31P 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 Kapp were in the order of 105 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 (Δσ) values determined by 31P 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 Tm 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 Tm 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.
AB - 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 (Tm) of lipids and on the mobility of phosphate head groups using Attenuated Total Reflection Fourier Transform Infrared-Red Spectroscopy (ATR-FTIR) and 31P 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 Kapp were in the order of 105 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 (Δσ) values determined by 31P 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 Tm 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 Tm 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.
KW - ATR-FTIR
KW - Ciprofloxacin
KW - Conformational analysis
KW - DPPC
KW - DPPG
KW - Melting temperature
KW - P NMR
KW - Steady-state fluorescence anisotropy
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U2 - 10.1016/j.bbamem.2008.08.015
DO - 10.1016/j.bbamem.2008.08.015
M3 - Article
C2 - 18809375
AN - SCOPUS:54049113756
SN - 0005-2736
VL - 1778
SP - 2535
EP - 2543
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 11
ER -