Toxicity and therapeutic efficacy of amphotericin B delivered through cholesterol hemisuccinate vesicles in the treatment of experimental murine aspergillosis.
We have studied the toxicity and therapeutic efficacy of amphotericin B in cholesterol hemisuccinate vesicles (ABCV) in the treatment of invasive aspergillosis in Balb/c mice. The toxicity of amphotericin B was significantly reduced when delivered through cholesterol hemisuccinate vesicles as compared to deoxycholate suspension (AmB(DOC)) as evidenced by reduced nephrotoxicity in Balb/c mice, lower in-vitro toxicity to erythrocytes and higher maximum tolerated dose. The latter increased from 2 mg/kg wt for AmB(DOC) to 17 mg/kg wt for ABCV. The vesicles had a mean diameter of 252 nm. In order to evaluate the therapeutic efficacy of ABCV, Aspergillus fumigatus-infected mice were treated with ABCV 2, 4, 8 or 12 mg/kg or AmB(DOC) 1 mg/kg wt. The antifungal activity was highly dependent on the dosage of ABCV on the basis of survival of treated mice and cfu in lung, liver, spleen and kidney. This study found that ABCV had dose-dependent antifungal activity and therapeutic efficacy in the treatment of invasive aspergillosis in Balb/c mice.
Saxena
S
S
Department of Biochemistry, University of Delhi South Campus, New Delhi, India.
Khan
J A
JA
Ghosh
P C
PC
D000666:Amphotericin B / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus; D002784:Cholesterol; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000935:Antifungal Agents; D000666:Amphotericin B; D002784:Cholesterol