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JAC Advance Access originally published online on December 20, 2005
Journal of Antimicrobial Chemotherapy 2006 57(2):349-352; doi:10.1093/jac/dki454
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Enhanced efficacy of pH-sensitive nystatin liposomes against Cryptococcus neoformans in murine model

Tahseen H. Nasti1, Masood A. Khan1,2 and M. Owais1,*

1 Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India; 2 Department of Immunology and Medical Microbiology, IUPUI, Indianapolis, IN, USA

Received 15 June 2005; returned 4 September 2005; revised 7 November 2005; accepted 15 November 2005

* Corresponding author. Tel: +91-571-2720388; Fax: +91-571-2721776; E-mail: owais_lakhnawi{at}yahoo.com

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


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