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The effect of aggregation state of amphotericin-B on its interactions with cholesterol- or ergosterol-containing phosphatidylcholine monolayers.

Abstract：

:Amphotericin B (AmB) is the most effective antibiotic used in the treatment of systemic fungal infections. It is generally thought that the activity of this drug results from its interaction with ergosterol, the main sterol of fungi membranes. However, AmB also interacts with cholesterol, the major sterol of mammal membranes, thus limiting the usefulness of this drug due to its relatively high toxicity. The aim of the present work is to study the molecular basis of the interactions of AmB with these sterols contained in a DOPC film by using the monolayer technique. Two different concentrations of the sterols in the film (13 and 30%) at an initial surface pressure of 30 mN/m were studied, which correspond to conditions found in various biological membranes. Four concentrations of AmB in the subphase, ranging from a molecularly dispersed to a highly aggregated state of the drug were studied. Our results show that the monomeric form of AmB interacts with the ergosterol containing film solely. On the other hand, when AmB is dispersed as a pre-micellar or as a highly aggregated state in the subphase, a very significant selectivity of its interactions between the two sterols is observed which is shown in our experimental results by a difference of 8 mN/m in the surface pressure when AmB interacts with ergosterol as compared to cholesterol. We show that the activity of AmB is most likely related to the micellar form of the antibiotic. In addition, we observe that upon increasing the amount of ergosterol in the film, the insertion of AmB is largely promoted, results that are discussed in terms of the molecular organization of the sterols within the monolayer film. We show that these results provide a better understanding of the action of AmB (activity/toxicity) at the membrane level.

journal_name

Chem Phys Lipids

journal_title

Chemistry and physics of lipids

authors

Barwicz J,Tancrède P

doi

10.1016/s0009-3084(96)02652-7

subject

Has Abstract

pub_date

1997-02-28 00:00:00

pages

145-55

issue

eissn

0009-3084

issn

1873-2941

pii

S0009-3084(96)02652-7

journal_volume

pub_type

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The effect of aggregation state of amphotericin-B on its interactions with cholesterol- or ergosterol-containing phosphatidylcholine monolayers.