Incorporation of amphotericin B in tuftsin-bearing liposomes showed enhanced efficacy against systemic cryptococcosis in leucopenic mice.
OBJECTIVE
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.
Khan
Masood A
MA
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India.
Nasti
Tahseen H
TH
Owais
M
M
D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D001921:Brain / Q000382:microbiology; D003453:Cryptococcosis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007155:Immunologic Factors / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects; D007970:Leukopenia / Q000150:complications*; D008081:Liposomes / Q000008:administration & dosage* / Q000378:metabolism; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D014405:Tuftsin / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*
D000935:Antifungal Agents; D007155:Immunologic Factors; D008081:Liposomes; C068538:liposomal amphotericin B; D000666:Amphotericin B; D014405:Tuftsin