Journal Article

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

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

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 4, pages 726-731
Published in print October 2005 | ISSN: 0305-7453
Published online August 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki307
Incorporation of amphotericin B in tuftsin-bearing liposomes showed enhanced efficacy against systemic cryptococcosis in leucopenic mice

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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 × 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

Journal Article.  4003 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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