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

Abstract

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 microg/mL) for three consecutive days prior to C. neoformans infection (7 x 10(5) 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.

• Authors: Masood A Khan, Tahseen H Nasti, M Owais
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 56 Issue 4 Pg. 726-31 (Oct 2005) ISSN: 0305-7453 [Print] England
• PMID: 16126780 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Immunologic Factors
• Liposomes
• liposomal amphotericin B
• Amphotericin B
• Tuftsin

Topics

• Amphotericin B (administration & dosage, chemistry)
• Animals
• Antifungal Agents (administration & dosage)
• Brain (microbiology)
• Cryptococcosis (complications, drug therapy, immunology)
• Dose-Response Relationship, Drug
• Drug Synergism
• Immunologic Factors (administration & dosage, chemistry, immunology)
• Leukocytes (drug effects)
• Leukopenia (complications)
• Liposomes (administration & dosage, metabolism)
• Lung (microbiology)
• Mice
• Mice, Inbred BALB C
• Tuftsin (administration & dosage, chemistry, immunology)