Treatment of Murine Cryptococcosis with Liposome-Associated Amphotericin B

Abstract

Liposomes were prepared to incorporate large amounts of amphotericin B. BALB/c mice were challenged with Cryptococcus neoformans and given liposome-associated amphotericin B (AMBL) or amphotericin B-deoxycholate (AMBD) intravenously. Mice that were treated with AMBL survived longer and had lower tissue counts of cryptococci than mice treated with AMBD or untreated control mice. The reduced acute toxicity of AMBL permitted much larger doses of amphotericin B to be given than were possible with AMBD. AMBL is a novel vehicle of administration that reduces toxicity and concentrates the drug in the appropriate target organs.

In vitro antifungal activities of amphotericin B and liposome-encapsulated amphotericin B

“…Amphotericin B concentrations 12-fold and greater than 50-fold higher were required to kill the same organism when cholesterol and ergosterol were incorporated into the liposomes. The addition of cholesterol to liposomes caused a significant increase in the minimal fungicidal concentration of amphotericin B in 7 of 19 other yeast strains tested, whereas ergosterol caused an increase in 18 of the 19 strains.Although there have been numerous reports on the use of liposome-encapsulated amphotericin B (L-AmpB) in the treatment of various infections in experimental animals (1,(4)(5)(6)8), this is the first report on the in vitro activity of LAmpB against various fungi. In the initial phase of this study, the lipid concentration of the liposomes was held constant with changing amphotericin B (AmpB) concentrations.…”

“…Although there have been numerous reports on the use of liposome-encapsulated amphotericin B (L-AmpB) in the treatment of various infections in experimental animals (1,(4)(5)(6)8), this is the first report on the in vitro activity of LAmpB against various fungi. In the initial phase of this study, the lipid concentration of the liposomes was held constant with changing amphotericin B (AmpB) concentrations.…”

“…These data are also difficult to explain. One possibility is that when AmpB is added to empty liposomes, the AmpB is concentrated in the outermost layers of the liposomes, thereby actually increasing the available drug concentrations to the fungal cell.Other investigators have used liposomal preparations containing sterols (1,6,8). AmpB binds to cholesterol present in mammalian cell membranes but has a much higher binding affinity for the ergosterol present in fungal membranes (3).…”

“…Other investigators have used liposomal preparations containing sterols (1,6,8). AmpB binds to cholesterol present in mammalian cell membranes but has a much higher binding affinity for the ergosterol present in fungal membranes (3).…”

Liposome-encapsulated amphotericin B in the treatment of experimental murine candidiasis.

“…In selecting a novel drug delivery system for amphotericin B, liposome was chosen to decrease its toxicity (Graybill et al 1982;LopezBerestein et al 1984).…”