Prevention by L-alpha-phosphatidylcholine of antifungal activity in vitro of liposome-encapsulated imidazoles determined by using time-killing curves

The antifungal activity of the imidazole derivatives miconazole and ketocon azole was reduced when they were entrapped in liposomal structures and sign ificant differences were detected between small unilamellar vesicles (SUV) and multilamellar vesicles (MLV). To understand which component of liposome s interfered with the antifungal activity of miconazole and ketoconazole, w e examined the influence of pure egg and soy L-alpha-phosphatidylcholine an d cholesterol on activity against Candida albicans ATCC E10231 by time kill ing curves. Association of phospholipids-cholesterol-imidazole leads to an inhibitory effect on the antifungal activity comparable to that shown when miconazole or ketoconazole were entrapped in SUV liposomes or when miconazo le and ketoconazole were incubated in the presence of L-alpha-phosphatidylc holine. The antifungal activity determined in the presence of cholesterol w as comparable to that observed with the free drugs. Inhibition of the antif ungal activity of miconazole and ketoconazole by phospholipids is dependent on the phospholipid concentration but is independent of the source of phos pholipids (egg or soy). Cholesterol had no influence on the antifungal acti vity of the imidazoles, unlike the effect on other antifungal drugs, such a s amphotericin B. (C) 2000 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.