Antileishmanial activity of nano-amphotericin B deoxycholate

J Antimicrob Chemother. 2008 Aug;62(2):376-80. doi: 10.1093/jac/dkn189. Epub 2008 May 2.

Abstract

Objectives: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / pharmacology
  • Amphotericin B / therapeutic use*
  • Amphotericin B / toxicity
  • Animals
  • Antiprotozoal Agents / administration & dosage
  • Antiprotozoal Agents / pharmacology
  • Antiprotozoal Agents / therapeutic use*
  • Antiprotozoal Agents / toxicity
  • Cell Line
  • Cricetinae
  • Deoxycholic Acid / administration & dosage
  • Deoxycholic Acid / pharmacology
  • Deoxycholic Acid / therapeutic use*
  • Deoxycholic Acid / toxicity
  • Drug Combinations
  • Leishmania donovani / drug effects*
  • Leishmaniasis, Visceral / drug therapy*
  • Macrophages / drug effects
  • Macrophages / parasitology
  • Mesocricetus
  • Mice
  • Nanoparticles*
  • Spleen / parasitology

Substances

  • Antiprotozoal Agents
  • Drug Combinations
  • Deoxycholic Acid
  • Amphotericin B
  • amphotericin B, deoxycholate drug combination