The effect of surfactants on the aggregation state of amphotericin B.
We have studied the effect of two surfactants, one non-ionic, lauryl sucrose (LS) and the other ionic, sodium deoxycholate (DOC), on the aggregation state of amphotericin B (AmB) and its selectivity towards ergosterol and cholesterol. It is shown that the addition of these surfactants has very similar effects on the AmB micelles. Below the critical micellar concentration of the surfactants, mixed micelles with AmB are first formed as a result of the penetration of the surfactant molecules into the AmB micelles. At higher concentrations of the surfactant molecules, the micellar structure is completely destroyed and AmB is found as monomers in solution. When the concentration of the surfactant is further increased, micelles of the surfactant molecules are built up, AmB remaining in monomeric form. However, the critical micellar concentration of LS is modified by the presence of AmB in solution, while that of DOC is not affected, thereby indicating that the interactions of AmB with LS are stronger than those of DOC with AmB. We also show that both surfactants enhance the selectivity of the AmB binding to sterols at exactly the concentrations of the surfactants which induce the monomerization of the antibiotic. It is observed that the maximal selectivity is found at a concentration of the surfactants corresponding to their particular CMC in presence of the antibiotic.
Tancrède
P
P
Département de Chimie-Biologie, Université du Québec à Trois-Rivières, Canada.
Barwicz
J
J
Jutras
S
S
Gruda
I
I
D000666:Amphotericin B / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D003840:Deoxycholic Acid / Q000378:metabolism*; D004875:Ergosterol / Q000378:metabolism; D007850:Lauric Acids / Q000378:metabolism*; D008823:Micelles; D013056:Spectrophotometry, Ultraviolet; D013501:Surface-Active Agents / Q000494:pharmacology*
D007850:Lauric Acids; D008823:Micelles; D013501:Surface-Active Agents; D003840:Deoxycholic Acid; C063467:lauryl sucrose; D000666:Amphotericin B; D002784:Cholesterol; D004875:Ergosterol