Selective toxicity and enhanced therapeutic index of liposomal polyene antibiotics in systemic fungal infections.
Incorporation of the polyene antibiotic amphotericin B (AMB) in liposomes results in a marked reduction in drug toxicity with no loss of antifungal potency. Nephrotoxicity, the dose-limiting side effect of AMB, is almost abolished when the drug is utilized in a liposomal carrier. Because of reduced toxicity, high doses of liposomal AMB can be used, resulting in superior therapy of systemic fungal infections in mice. The improved therapeutic index of liposomal AMB versus free AMB is also manifest in infected neutropenic animals. The reduced toxicity of liposomal AMB is due to a fundamental alteration in the interaction of the drug with mammalian cell membranes. AMB transfers effectively from donor liposomes to fungal cell walls and membranes and is thus toxic to fungi. By contrast, AMB does not transfer from liposomes to mammalian cells and thus is not toxic to these cells. Thus, the use of liposomal AMB may offer a marked improvement in the therapy of systemic fungal infection in cancer patients and other immunodebilitated individuals.
D000666:Amphotericin B / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D002177:Candidiasis / Q000188:drug therapy; D002784:Cholesterol / Q000008:administration & dosage; D004875:Ergosterol / Q000008:administration & dosage; D005658:Fungi / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects; D008081:Liposomes / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D010743:Phospholipids / Q000008:administration & dosage; D013329:Structure-Activity Relationship
D008081:Liposomes; D010743:Phospholipids; D000666:Amphotericin B; D002784:Cholesterol; D004875:Ergosterol