Abstract
The therapeutic activity of nystatin (NYS) incorporated in multilamellar liposomes (L-NYS) was studied in vivo. Hale-Stoner mice injected intravenously with various doses of L-NYS and free NYS showed a significant reduction in toxicity of NYS after the NYS was incorporated into liposomes (maximal tolerated doses, 16 and 4 mg/kg of body weight, respectively). The maximal tolerated dose of free NYS had no effect in the treatment of mice infected with Candida albicans, whereas L-NYS at an equivalent dose improved the survival of mice. A marked increase in survival was observed when L-NYS was administered in higher and multiple doses (total doses up to 80 mg/kg). Liposome encapsulation thus provided a means for intravenous administration of NYS, reducing its toxicity and making it an active systemic antifungal agent.
Highlights
The therapeutic activity of nystatin (NYS) incorporated in multilamellar liposomes (L-NYS) was studied in vivo
The maximal tolerated dose of free NYS had no effect in the treatment of mice infected with Candida albicans, whereas L-NYS at an equivalent dose improved the survival of mice
We have recently demonstrated that liposome encapsulation improves the therapeutic index of amphotericin B both against experimental murine candidiasis [10, 11] and in the treatment of fungal infections in patients with leukemia and lymphoma [9]
Summary
The therapeutic activity of nystatin (NYS) incorporated in multilamellar liposomes (L-NYS) was studied in vivo. The maximal tolerated dose of free NYS had no effect in the treatment of mice infected with Candida albicans, whereas L-NYS at an equivalent dose improved the survival of mice. The hydrophobic nature of nystatin (NYS) has precluded its systemic administration It has been used as suspensions prepared in various ways and administered to patients orally [1, 2, 7, 14, 17]. Most of these studies failed to document a beneficial effect of NYS administration against systemic fungal infections [2, 14, 17]. The present communication reports on the in vivo toxicity and antifungal efficacy of L-NYS as compared with those of the free drug
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