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-liposomal amphotericin B were compared in cultured epidermal Langerhans cells infected with Candida glabrata. Uptake of the yeast was determined by light and electron microscopy, and viability was assessed by plating dilutions of lysates from yeast-infected Langerhans cells and counting colony forming units. The Candida-infected Langerhans cells were incubated for 6, 24 or 48 h with 12.5 micro ml-1 of AmBisome or non-liposomal amphotericin B, non-drug-containing liposomes or media. Intracellular C. glabrata incubated with media or non-drug-containing liposomes showed a 2 log increase in cfu, and microscopic examination revealed budding yeast within the Langerhans cells. Both liposomal and non-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 with non-liposomal amphotericin B were characterized by the absence of intact organelles, disrupted non-granular cytoplasm and the presence of many large vacuoles. In conclusion, AmBisome was significantly less toxic for epidermal Langerhans cells than amphotericin B, but demonstrated 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.
Sperry
P J
PJ
Biological Sciences Department, California State Polytechnic University, Pomona, California 91768, USA.
Cua
D J
DJ
Wetzel
S A
SA
Adler-Moore
J P
JP
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D007801:Langerhans Cells / Q000187:drug effects / Q000382:microbiology* / Q000648:ultrastructure; D008081:Liposomes; D051379:Mice
D000935:Antifungal Agents; D008081:Liposomes; C068538:liposomal amphotericin B; D000666:Amphotericin B