title: In vitro effect of new formulations of amphotericin B on amastigote and promastigote forms of Leishmania infantum.
abstract: The in vitro antileishmanial activities of various new amphotericin B (AMB) formulations were investigated, including microspheres of hydrophilic albumin with three AMB aggregation forms (monomeric, dimeric and multiaggregate) and the polymers of polylactic-co-glycolic acid, Resomer RG502 and RG503 with the multiaggregate AMB form. This in vitro study was performed on the extracellular promastigote form and the intracellular amastigote form of a canine strain of Leishmania infantum (UCM 20) using the infected J774 murine macrophage-like cell line. Albumin-encapsulated forms did not show any toxicity for murine cells and had lower median effective concentration (EC50) values (ca. 0.003 microg/mL) for L. infantum amastigotes than free formulations (0.03 microg/mL). In addition, the aggregation state of AMB had a notable effect on the antileishmanial activity of the drug. Results obtained in vitro point towards interest in monomeric AMB encapsulated in microspheres in the chemotherapeutic control of leishmaniasis.
authors.affiliation: Department of Animal Health, Faculty of Veterinary Medicine, Avda. Puerta de Hierro s/n, Complutense University, Madrid 28040, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Ordóñez-Gutiérrez
authors.forename: Raquel
authors.initials: R
authors.lastname: Espada-Fernández
authors.forename: María Auxiliadora
authors.initials: MA
authors.lastname: Dea-Ayuela
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Torrado
authors.forename: Francisco
authors.initials: F
authors.lastname: Bolás-Fernandez
authors.forename: José María
authors.initials: JM
authors.lastname: Alunda
mesh_terms: D000418:Albumins / Q000494:pharmacology; D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D006016:Glycolates / Q000494:pharmacology; D019344:Lactic Acid; D018314:Leishmania infantum / Q000187:drug effects* / Q000254:growth & development; D008018:Life Cycle Stages / Q000187:drug effects; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008863:Microspheres; D021261:Parasitic Sensitivity Tests; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000418:Albumins; D000981:Antiprotozoal Agents; D006016:Glycolates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000666:Amphotericin B