title: In vitro antileishmanial activity of amphotericin B loaded in poly(epsilon-caprolactone) nanospheres.
abstract: The activity of formulations for amphotericin B (AmB) associated with poly(epsilon-caprolactone) nanospheres and coated with variable amounts of a non ionic surfactant poloxamer 188, was evaluated against AmB-susceptible (WT) and AmB-resistant (AmB(r)) strains of Leishmania donovani amastigotes in thioglycolate-elicited peritoneal macrophages. AmB-nanospheres were more actives than free AmB only against amastigotes of wild strain. The activity was not influenced by the concentration of poloxamer 188 used to stabilize the nanospheres in spite of this surfactant was previously reported to synergy with AmB on the membrane of the resistant parasite. Similarly, this improvement was not mediated through macrophage activation. In fact, these nanoparticle formulations appeared to inhibit both NO and TNF-alpha production induced by the free drug. Therefore, we suggest that the association of AmB with nanospheres may improve the capability of the drug to interact with ergosterol. This hypothesis appears to be supported by the fact that nanospheres did not show any improvement of the AmB activity against the resistant strain (characterized by the absence of ergosterol).
authors.affiliation: Centro Galénico, Facultad de Farmacia, Universidad de Navarra, Pamplona, 31080 Spain.
authors.forename: M S
authors.initials: MS
authors.lastname: Espuelas
authors.forename: P
authors.initials: P
authors.lastname: Legrand
authors.forename: P M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: C
authors.initials: C
authors.lastname: Bories
authors.forename: G
authors.initials: G
authors.lastname: Barratt
authors.forename: J M
authors.initials: JM
authors.lastname: Irache
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide; D004351:Drug Resistance; D005079:Excipients; D007893:Leishmania donovani / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D008863:Microspheres; D008928:Mitochondria / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D005079:Excipients; D011091:Polyesters; D014409:Tumor Necrosis Factor-alpha; C016240:polycaprolactone; D009569:Nitric Oxide; D000666:Amphotericin B; D004121:Dimethyl Sulfoxide