Polyene antibiotics stability

The statement that polyene antibiotics exhibit poor stability to heat, UV radiation and extremes of pH is often made [34,79—81]. When pure dry antibiotic is stored in the dark at low temperature, potency will not be lost, even over long periods [82,83]. Stability to light and temperature decreases as the aze of the chromophore increases. 

The stability of bilayers in the presence of polyene antibiotics has been investigated [199]. Pure lecithin bilayers were found to be stable in the presence of 40 /xM filipin or nystatin in contrast, bilayers consisting of equal parts cholesterol and lecithin were disrupted rapidly by filipin but considerably more slowly by nystatin. Bilayers consisting exclusively of cholesterol or bilayers with phospholipid sterol ratios of 10 1 were stable in the presence of filipin. When added to a sterol-containing lecithin bilayer, filipin removed the sterol from the membrane by non-polar association, changing the fluidity of the lipid chains in the bilayer, and ultimately caused membrane breakdown [200],... 

The instability of polyenes should not be overstated the dry product is relatively stable and it has been shown that aqueous solutions of polyenes are stable at least for 24 h even when exposed to light, air and room temperatures [88—90]. When dissolved in aqueous systems, the antibiotic consists of a micellar dispersion held together by hydrophobic forces. This may confer a degree of protection in that the sensitive region of the antibiotic exists in a localised hydrophobic environment shielded from physical and chemical damage. When stored under identical conditions, dry amphotericin B and amphotericin B methyl ester exhibited similar stability. In aqueous solution, amphotericin B was more stable than its methyl ester. Spectrophotometric studies [91] have shown that in aqueous solutions amphotericin methyl ester was more dispersed than the parent compound and it appeared that increased water solubility was accompanied by increased vulnerability to damage [92]. 

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