title: Mixed formulation of conventional and pegylated liposomes as a novel drug delivery strategy for improved treatment of visceral leishmaniasis.
abstract: OBJECTIVE
  Test the hypothesis that pegylated meglumine antimoniate-containing liposomes (LMA) and their mixture with non-pegylated (conventional) LMA may be more effective than conventional LMA against visceral leishmaniasis (VL), because of wider drug distribution among different mononuclear phagocyte system (MPS) tissues.
  
  
  METHODS
  Sb was determined in the blood and MPS tissues after administration of pegylated or conventional LMA intravenously to mongrel dogs naturally infected with Leishmania infantum and Swiss mice. Pegylated and conventional LMA as well as their mixture were evaluated for their antileishmanial efficacy in BALB/c infected with L. infantum through determination of parasite load in liver, spleen and bone marrow.
  
  
  RESULTS
  An improved targeting of Sb to the bone marrow of dogs was clearly evidenced, as an important impact of pegylation. In accordance with this data, pegylated LMA significantly reduced parasite load in bone marrow of infected mice, in contrast to conventional LMA. The mixed formulation of conventional and pegylated LMA promoted parasite suppression to a higher extent in both spleen and bone marrow, compared to pegylated or conventional LMA.
  
  
  CONCLUSIONS
  The present work establishes for the first time the potential of mixed formulations of conventional and pegylated liposomes as a drug delivery strategy for improved treatment of VL.
authors: Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Fisiologia e Biofísica , Av. Antônio Carlos 6627, Pampulha, 31270-901 Belo Horizonte, Minas Gerais , Brazil +55 31 34092940 ; +55 31 34092924 ; frezard@icb.ufmg.br.
authors: Erly G
authors: EG
authors: Azevedo
authors: Raul R
authors: RR
authors: Ribeiro
authors: Sydnei M
authors: SM
authors: da Silva
authors: Cláudio S
authors: CS
authors: Ferreira
authors: Ligia E
authors: LE
authors: de Souza
authors: Adriel Af
authors: AA
authors: Ferreira
authors: Renata A
authors: RA
authors: de Oliveira E Castro
authors: Cynthia
authors: C
authors: Demicheli
authors: Simone A
authors: SA
authors: Rezende
authors: Frédéric
authors: F
authors: Frézard
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001853:Bone Marrow / Q000469:parasitology; D002626:Chemistry, Pharmaceutical; D004283:Dog Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000469:parasitology; D004285:Dogs; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D018314:Leishmania infantum / Q000302:isolation & purification* / Q000472:pathogenicity; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000378:metabolism* / Q000469:parasitology / Q000662:veterinary; D008081:Liposomes / Q000737:chemistry*; D008099:Liver / Q000469:parasitology; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D059208:Parasite Load; D011092:Polyethylene Glycols / Q000737:chemistry*; D013154:Spleen / Q000469:parasitology
chemical_list: D000981:Antiprotozoal Agents; D004337:Drug Carriers; D008081:Liposomes; D009942:Organometallic Compounds; D011092:Polyethylene Glycols; D008536:Meglumine; D000077485:Meglumine Antimoniate
keywords: antimony; dogs; leishmaniasis; liposomes; pharmacokinetics; visceral leishmaniasis