Skip Navigation



JAC Advance Access published online on December 8, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh522
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
55/2/223    most recent
dkh522v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Khan, M. A.
Right arrow Articles by Mohammad, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Khan, M. A.
Right arrow Articles by Mohammad, O.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

JAC © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved
Received July 6, 2004
Revised October 29, 2004
Accepted November 1, 2004

Original article

Enhanced anticryptococcal activity of chloroquine in phosphatidylserine-containing liposomes in a murine model

Masood A. Khan 1*, Rukhsana Jabeen 1, T. H. Nasti 1, and Owais Mohammad 1

1 Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India

* To whom correspondence should be addressed.
Masood A. Khan, E-mail: alammasood1{at}rediffmail.com


  Abstract

Objectives: The anticryptococcal activity of chloroquine was assessed after incorporation in phosphatidylserine (PS)-containing negatively charged liposomes in a murine model.

Methods: In the present study, we investigated the antifungal activity of chloroquine entrapped in PS liposomes against Cryptococcus neoformans in the macrophage cell line J 774 and in a murine model. Mice were treated with free as well as liposomal formulations of chloroquine before and after challenging with C. neoformans infection. The anticryptococcal activity of chloroquine was also evaluated in combination with fluconazole in the treatment of systemic murine cryptococcosis. The efficacy of chloroquine treatment was assessed by continued survival as well as by colony forming units (cfu) in liver and brain of treated mice.

Results: Chloroquine entrapped in PS liposomes shows increased activity against C. neoformans infection both in in vitro and in vivo studies. Moreover, the antifungal activity of fluconazole increases when used in combination with liposomal chloroquine. Chloroquine in PS liposomes was found to be more effective in comparison with the same dose of free chloroquine or chloroquine entrapped in neutral liposomes.

Conclusions: The enhanced anticryptococcal activity of chloroquine in PS liposomes seems to be due to uptake of drug-containing PS liposomes by macrophages. It can be assumed that liposome-mediated delivery of chloroquine to macrophages results in an unfavourable (alkaline) environment for the growth of C. neoformans inside macrophages.

Keywords: Cryptococcus neoformans; fluconazole; macrophages; therapy.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Infect. Immun.Home page
T. B. Kechichian, J. Shea, and M. Del Poeta
Depletion of Alveolar Macrophages Decreases the Dissemination of a Glucosylceramide-Deficient Mutant of Cryptococcus neoformans in Immunodeficient Mice
Infect. Immun., October 1, 2007; 75(10): 4792 - 4798.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.