Interaction of the macrolide antibiotic azithromycin with lipid bilayers: effect on membrane organization, fluidity, and permeability.
OBJECTIVE
To investigate the effect of a macrolide antibiotic, azithromycin, on the molecular organization of DPPC:DOPC, DPPE:DOPC, SM:DOPC, and SM:Chol:DOPC lipid vesicles as well as the effect of azithromycin on membrane fluidity and permeability.


METHODS
The molecular organization of model membranes was characterized by atomic force microscopy (AFM), and the amount of azithromycin bound to lipid membranes was determined by equilibrium dialysis. The membrane fluidity and permeability were analyzed using fluorescence polarization studies and release of calcein-entrapped liposomes, respectively.


RESULTS
In situ AFM images revealed that azithromycin leads to the erosion and disappearance of DPPC and DPPE gel domains, whereas no effect was noted on SM and SM:cholesterol domains. Although azithromycin did not alter the permeability of DPPC:DOPC, DPPE:DOPC, SM:DOPC, and SM:Chol:DOPC lipid vesicles, it increased the fluidity at the hydrophilic/hydrophobic interface in DPPC:DOPC and DPPE:DOPC models. This effect may be responsible for the ability of azithromycin to erode the DPPC and DPPE gel domains, as observed by AFM.


CONCLUSIONS
This study shows the interest of both AFM and biophysical methods to characterize the drug-membrane interactions.
Berquand
A
A
Unité de Chimie des Interfaces, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium.
Fa
N
N
Dufrêne
Y F
YF
Mingeot-Leclercq
M P
MP
D000900:Anti-Bacterial Agents / Q000378:metabolism; D017963:Azithromycin / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology*; D008051:Lipid Bilayers / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism*; D018942:Macrolides / Q000378:metabolism; D008560:Membrane Fluidity / Q000502:physiology*
D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D008081:Liposomes; D018942:Macrolides; D017963:Azithromycin