AmBisome targeting to fungal infections.

AmBisome is a small unilamellar liposome preparation (45-80 nm) containing amphotericin B in the bilayer. The reduced toxicity and elevated peak plasma level of AmBisome compared with amphotericin B is achieved without loss of the broad-spectrum antifungal activity of amphotericin B. Various investigators have documented its efficacy in treating systemic fungal infections. When in vitro and in vivo studies were done to elucidate the antifungal mechanism of action of AmBisome, the results showed that there was a direct interaction between AmBisome and fungi. Freeze-fracture electron microscopy, fluorescently-labeled liposomes and gold-labeled liposomes were used in these studies. Fluorescence microscopy and electron microscopy showed that AmBisome and liposomes, with the same lipid composition, but without drug, targeted to fungi in vitro. Intact liposomes of either type could be seen attached to the outer surface of the fungal cell wall within an hour after exposure to the liposomes. Only AmBisome was disrupted by this interaction resulting in death of the fungi to which the AmBisome had bound. As the fungal cells died, lipid from the AmBisome could be detected in the cytoplasm. Liposomes without drug remained intact on the surface of viable fungi for prolonged periods of time. When fluorescently-labeled liposomes with or without drug were injected into Candida-infected mice, the results showed bright fluorescence localized at the sites of fungal infection. The in vitro data suggest that only the AmBisome could kill the fungus growing in vivo and that the antifungal efficacy of AmBisome was related to its ability to target to fungi.