POLYENE ANTIBIOTICS AS MEMBRANE-ACTIVE AGENTS

The observation that polyenes alter the selective permeability properties of eukaryote membranes [101] has resulted in extensive studies on the interaction between polyenes and the sterol component of membranes. Valuable information on the mechanism of polyene—membrane interaction has been obtained not only from intact cell membranes and membranes derived from cells but also from artificial membrane systems of known lipid composition. 

Sterol-supplemented liposomes were able to bind and alter the UV absorption spectra of filipin, etruscomycin and amphotericin B but not those of nystatin or pimaricin [146]. The presence of a 30-hydroxyl group in the sterol incorporated into the liposome appeared to be a prerequisite for interaction with polyene antibiotics. Sterol-containing liposomes have been shown to enhance the fluorescence intensity of filipin and etruscomycin [157,186]. 

The nature of the interaction between polyene antibiotics and membrane sterols has also been investigated using UV, fluorescence and circular dichroism spectral studies [155,159,187,188]. The rate and degree of filipin III binding to cholesterol-containing liposomes depended upon the absolute sterol concentration and the mole percent in the bilayer. Binding constants for filipin III and liposomes were also estimated. 

Liposomes, prepared by extracting naturally occurring membranes of A. laidlawii grown with and without sterol, possessed permeability properties comparable with those of parent cells [152]. To reduce the permeability of the liposome, the sterol must possess a planar sterol ring and 30-hydroxyl group [179, 

The polyene sterol interaction did not merely nullify the effect of sterol addition. Polyenes appeared to combine with liposome sterols and this combination destroyed the permeability properties of the liposome. 

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