Journal Article

Enhanced efficacy of pH-sensitive nystatin liposomes against <i>Cryptococcus neoformans</i> in murine model

Tahseen H. Nasti, Masood A. Khan and M. Owais

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 57, issue 2, pages 349-352
Published in print February 2006 | ISSN: 0305-7453
Published online December 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki454
Enhanced efficacy of pH-sensitive nystatin liposomes against Cryptococcus neoformans in murine model

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  • Medical Oncology
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Objectives: To evaluate the efficacy of pH-sensitive liposomes of nystatin against Cryptococcus neoformans infection in a murine model.

Methods: In the present study, we investigated the antifungal activity of nystatin entrapped in pH-sensitive liposomes in a murine model. Mice infected with C. neoformans were treated with nystatin in neutral egg phosphatidylcholine (egg-PC) liposomes, as well as pH-sensitive nystatin liposomes. The anticryptococcal efficacy of liposomal formulations of nystatin was assessed by continued survival and colony-forming units (cfu) in liver and brain of the treated mice.

Results: pH-sensitive liposomes of nystatin showed better efficacy compared with its free or egg-PC liposome form against C. neoformans infection in BALB/c mice. Mice treated with pH-sensitive nystatin liposomes showed 80% survival with less fungal burden in liver and brain of treated mice. However, there was only 40% survival in the group of animals treated with egg-PC liposome-intercalated nystatin, whereas its free form had poor efficacy with 20% survival.

Conclusions: The enhanced anticryptococcal efficacy of the pH-sensitive nystatin liposomes can be attributed to the pH-dependent release of the drug in the low pH environment of lysosomes. The destabilization of the pH-sensitive liposomes in the acidic environment of macrophages results in the site-specific targeting of nystatin that improves its intracellular antifungal activity.

Keywords: lysosomes; drug delivery pH-sensitive liposomes

Journal Article.  2884 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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