ANTIMICROBIAL ACTIVITY OF AMBISOME AND NON-LIPOSOMAL AMPHOTERICIN-B FOLLOWING UPTAKE OF CANDIDA-GLABRATA BY MURINE EPIDERMAL LANGERHANS CELLS

The antifungal efficacy and cellular toxicity of AmBisome(R) and non-l iposomal amphotericin B were compared in cultured epidermal Langerhans cells infected with Candicia glabrata. Uptake of the yeast was determ ined by light and electron microscopy, and viability was assessed by p lating dilutions of lysates from yeast-infected Langerhans cells and c ounting colony forming units. The Candida-infected Langerhans cells we re incubated for 6, 24 or 48 h with 12.5 mu g ml(-1) of AmBisome or no n-liposomal amphotericin B, non-drug-containing liposomes or media. In tracellular C. glabrata incubated with media or non-drug-containing li posomes showed a 2 log increase in cfu, and microscopic examination re vealed budding yeast within the Langerhans cells. Both liposomal and n on-liposomal amphotericin B treatment reduced intracellular growth of C. glabrata by 5 logs over 48 h of incubation. A morphometric analysis of cell ultrastructure demonstrated that AmBisome-treated Langerhans cells retained their cell architecture, but Langerhans cells treated w ith non-liposomal amphotericin B were characterized by the absence of intact organelles, disrupted non-granular cytoplasm and the presence o f many large vacuoles. In conclusion, AmBisome was significantly less toxic for epidermal Langerhans cells than amphotericin B, but demonstr ated comparable antifungal efficacy. After 48 h of drug exposure, both forms of amphotericin B effectively inhibited intracellular growth of C. glabrata, but only AmBisome did not damage the Langerhans cells.