title: Lipid-based nanoformulations of trifluralin analogs in the management of Leishmania infantum infections.
abstract: OBJECTIVE
  To improve the potential of trifluralin (TFL) in the management of Leishmania infantum infections through the synthesis of analogs (TFLA) and incorporation in nanoparticulate drug delivery systems (NanoDDS), liposomes and solid lipid nanoparticles, for selective targeting to leishmania infection sites.
  
  
  METHODS
  In vitro screening of 18 TFLA was performed by flow cytometry. NanoDDS were loaded with active TFLA and evaluated for antileishmanial efficacy in mice through determination of parasite burden in liver and spleen.
  
  
  RESULTS
  The in vitro testing revealed the most active and nontoxic TFLAs, which were selected for the in vivo studies based on high incorporation in liposomes and lipid nanoparticles (>90%). Selected TFLA nanoformulations showed superior antileishmanial activity in mice (parasite burden >80%), over free TFLA and Glucantime.
  
  
  CONCLUSIONS
  The modification of TFL structure to obtain active TFLA, together with their incorporation in NanoDDS, improved their in vivo performance against L. infantum infection.
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Lopes
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Pereira
authors.affiliation: Solar Energy Unit, National Laboratory for Energy & Geology, Estrada do Paço do Lumiar, 22, 1649-038 Lisboa, Portugal.
authors.forename: M Alexandra
authors.initials: MA
authors.lastname: Esteves
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: M Manuela
authors.initials: MM
authors.lastname: Gaspar
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Manuela
authors.initials: M
authors.lastname: Carvalheiro
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Carla V
authors.initials: CV
authors.lastname: Eleutério
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Lídia
authors.initials: L
authors.lastname: Gonçalves
authors.affiliation: Departamento de Biología de Sistemas-Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: António
authors.initials: A
authors.lastname: Jiménez-Ruiz
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: António J
authors.initials: AJ
authors.lastname: Almeida
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: M Eugénia M
authors.initials: ME
authors.lastname: Cruz
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000737:chemistry; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D018314:Leishmania infantum / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D010316:Particle Size; D016896:Treatment Outcome; D014274:Trifluralin / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D000981:Antiprotozoal Agents; D008081:Liposomes; D053769:Nanocapsules; D014274:Trifluralin
keywords: dinitroanilines; drug delivery; drug development; in vitro activity; in vivo activity; leishmaniasis; liposomes; solid lipid nanoparticles; trifluralin