1: Pharm Res. 2005 Mar;22(3):465-75. 

Interaction of the macrolide antibiotic azithromycin with lipid bilayers: effect
on membrane organization, fluidity, and permeability.

Berquand A, Fa N, Dufrene YF, Mingeot-Leclercq MP.

Unite de Chimie des Interfaces, Universite Catholique de Louvain, B-1348
Louvain-la-Neuve, Belgium.

PURPOSE: 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.

PMID: 15835753 [PubMed - in process]