Antileishmanial activity of nano-amphotericin B deoxycholate.
OBJECTIVE
The aim of the present study was to compare the efficacy of a nano form of amphotericin B deoxycholate with that of conventional amphotericin B deoxycholate for the treatment of visceral leishmaniasis.


METHODS
We have formulated nanoparticles (10-20 nM) from amphotericin B deoxycholate (1-2 microM) by applying high-pressure (150 argon) milling homogenization and have tested their efficacy in a J774A cell line and in hamsters. Parasite survival and tissue burden in spleen were evaluated for nano-amphotericin B and conventional amphotericin B. Both nano-amphotericin B and conventional amphotericin B were injected intraperitoneally at 5 mg/kg per day for 5 days.


RESULTS
The inhibition of amastigotes in the splenic tissue with nano-amphotericin B was significantly more than with conventional amphotericin B (92.18% versus 74.57%, P = 0.005). Similarly, the suppression of parasite replication in the spleen was also found to be significant (99.18% versus 97.17%, P = 0.05). In a cytotoxicity test, nano-amphotericin B against the J774A cell line had a CC(50) of 12.67 mg/L in comparison with 10.61 mg/L for amphotericin B, far higher than the doses used for ED(50).


CONCLUSIONS
Nanoparticles of amphotericin B had significantly greater efficacy than conventional amphotericin B. This formulation may have a favourable safety profile, and if production costs are low, it may prove to be a feasible alternative to conventional amphotericin B.
Manandhar
Krishna Das
KD
Infectious Disease Research Laboratory, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India.
Yadav
Thakur Prasad
TP
Prajapati
Vijay Kumar
VK
Kumar
Subodh
S
Rai
Madhukar
M
Dube
Anuradha
A
Srivastava
Onkar Nath
ON
Sundar
Shyam
S
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002460:Cell Line; D006224:Cricetinae; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D004338:Drug Combinations; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008647:Mesocricetus; D051379:Mice; D053758:Nanoparticles; D013154:Spleen / Q000469:parasitology
D000981:Antiprotozoal Agents; D004338:Drug Combinations; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination