Enhanced efficacy of pH-sensitive nystatin liposomes against Cryptococcus neoformans in murine model.
OBJECTIVE
To evaluate the efficacy of pH-sensitive liposomes of nystatin against Cryptococcus neoformans infection in a murine model.


METHODS
In the present study, we investigated the antifungal activity of nystatin entrapped in pH-sensitive liposomes in a murine model. Mice infected with C. neoformans were treated with nystatin in neutral egg phosphatidylcholine (egg-PC) liposomes, as well as pH-sensitive nystatin liposomes. The anticryptococcal efficacy of liposomal formulations of nystatin was assessed by continued survival and colony-forming units (cfu) in liver and brain of the treated mice.


RESULTS
pH-sensitive liposomes of nystatin showed better efficacy compared with its free or egg-PC liposome form against C. neoformans infection in BALB/c mice. Mice treated with pH-sensitive nystatin liposomes showed 80% survival with less fungal burden in liver and brain of treated mice. However, there was only 40% survival in the group of animals treated with egg-PC liposome-intercalated nystatin, whereas its free form had poor efficacy with 20% survival.


CONCLUSIONS
The enhanced anticryptococcal efficacy of the pH-sensitive nystatin liposomes can be attributed to the pH-dependent release of the drug in the low pH environment of lysosomes. The destabilization of the pH-sensitive liposomes in the acidic environment of macrophages results in the site-specific targeting of nystatin that improves its intracellular antifungal activity.
Nasti
Tahseen H
TH
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
Khan
Masood A
MA
Owais
M
M
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001921:Brain / Q000382:microbiology; D003453:Cryptococcosis / Q000188:drug therapy* / Q000382:microbiology; D004337:Drug Carriers; D006863:Hydrogen-Ion Concentration; D007364:Intercalating Agents; D008081:Liposomes; D008099:Liver / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009761:Nystatin / Q000008:administration & dosage* / Q000627:therapeutic use*; D010713:Phosphatidylcholines; D016019:Survival Analysis
D000935:Antifungal Agents; D004337:Drug Carriers; D007364:Intercalating Agents; D008081:Liposomes; D010713:Phosphatidylcholines; D009761:Nystatin