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Antileishmanial efficacy of amphotericin B bearing emulsomes against experimental visceral leishmaniasis.

Abstract
Amphotericin B (AmB) was formulated in trilaurin-based emulsomes (nanosize lipid particles) stabilized by soya phosphatidylcholine (PC), as a new delivery system for macrophage targeting for the treatment of visceral leishmaniasis (VL). Emulsomes were modified by coating them with macrophage-specific ligand (O-palmitoyl mannan, OPM). The antileishmanial activity of AmB-deoxycholate (AmB-Doc) and emulsome entrapped AmB was tested in vitro in Leishmania donovani infected macrophage-amastigote system (J774A.1 cells), which showed higher efficacy of OPM grafted AmB emulsomes (TLEs-OPM) over plain AmB emulsomes (TLEs) and AmB-Doc. The in vivo antileishmanial activity of the AmB (0.5 mg/kg) was tested in AmB-Doc, TLEs and TLEs-OPM forms against VL in L. donovani infected hamsters. Formulation TLEs-OPM eliminated intracellular amastigotes of L. donovani within splenic macrophages more efficiently (73.7 +/- 6.7% parasite inhibition) than the formulation TLEs (51.7 +/- 5.4% parasite inhibition) (P < 0.01) or AmB-Doc (30.4 +/- 4.8% parasite inhibition) (P < 0.001). Our results suggest that these newer formulations (plain and ligand appended emulsomes) are a promising alternative to the conventional AmB-Doc formulation for the treatment of VL.
AuthorsSwati Gupta, Anuradha Dube, Suresh P Vyas
JournalJournal of drug targeting (J Drug Target) Vol. 15 Issue 6 Pg. 437-44 (Jul 2007) ISSN: 1061-186X [Print] England
PMID17613662 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Drug Carriers
  • Drug Combinations
  • Trypanocidal Agents
  • Deoxycholic Acid
  • Amphotericin B
  • amphotericin B, deoxycholate drug combination
Topics
  • Amphotericin B (administration & dosage, therapeutic use)
  • Animals
  • Cricetinae
  • Deoxycholic Acid (administration & dosage, therapeutic use)
  • Disease Models, Animal
  • Drug Carriers
  • Drug Combinations
  • Leishmania donovani (drug effects)
  • Leishmaniasis, Visceral (drug therapy, parasitology)
  • Macrophages (drug effects, parasitology)
  • Male
  • Mesocricetus
  • Mice
  • Nanoparticles
  • Trypanocidal Agents (administration & dosage, therapeutic use)

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