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JAC Advance Access originally published online on August 26, 2005
Journal of Antimicrobial Chemotherapy 2005 56(4):726-731; doi:10.1093/jac/dki307
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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

Incorporation of amphotericin B in tuftsin-bearing liposomes showed enhanced efficacy against systemic cryptococcosis in leucopenic mice

Masood A. Khan1,2, Tahseen H. Nasti1 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 14 May 2005; returned 11 June 2005; revised 26 July 2005; accepted 29 July 2005

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

Objectives: The role of the immunomodulator tuftsin in enhancing the antifungal activity of liposomal amphotericin B against Cryptococcus neoformans in leucopenic mice was assessed.

Methods: In the present study, we investigated the antifungal activity of amphotericin B liposomes with tuftsin grafted on the surface. Mice were treated with free amphotericin B as well as liposomal formulations after C. neoformans infection. For prophylactic studies, mice were pre-treated with liposomal tuftsin (50 µg/mL) for three consecutive days prior to C. neoformans infection (7 x 105 cfu/mouse). Chemotherapy, with tuftsin-free and tuftsin-bearing amphotericin B liposomes, was started 24 h post C. neoformans infection. The role of tuftsin in immunoaugmentative therapy was assessed by survival and cfu of treated mice.

Results: Amphotericin B entrapped in tuftsin-bearing liposomes showed increased anticryptococcal activity in the murine model. Moreover, tuftsin pre-treatment further augmented the antifungal activity of liposomal amphotericin B in leucopenic mice. Incorporation of tuftsin in liposomes resulted in increased anticryptococcal activity of liposomal amphotericin B compared with amphotericin B deoxycholate and conventional liposomal amphotericin B formulations.

Conclusions: The enhanced anticryptococcal activity of amphotericin B in tuftsin-liposomes can be attributed to the immune-stimulating property of tuftsin. Tuftsin activates the key immune cells, due to the presence of its receptors on macrophages and neutrophils, for a better fight against pathogens. Simultaneous liposome-mediated delivery of amphotericin B to the site of infection kills the pathogens more effectively.

Keywords: immunomodulators , leucocytes , prophylaxis


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