title: 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.
authors.affiliation: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr Hari Singh Gour Vishwavidyalaya, Sagar, MP, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Gupta
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dube
authors.forename: Suresh P
authors.initials: SP
authors.lastname: Vyas
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000627:therapeutic use*; D000818:Animals; D006224:Cricetinae; D003840:Deoxycholic Acid / Q000008:administration & dosage* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004337:Drug Carriers; D004338:Drug Combinations; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D053758:Nanoparticles; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D004337:Drug Carriers; D004338:Drug Combinations; D014344:Trypanocidal Agents; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination