title: In vivo proinflammatory activity of generations 0-3 (G0-G3) polyamidoamine (PAMAM) nanoparticles.
abstract: OBJECTIVE
  The aim of this study was to determine whether different generations (G) polyamidoamine (PAMAM) dendrimers possess proinflammatory activities in vivo.
  
  
  METHODS
  Several hundred female CD-1 mice were used to test four different PAMAM dendrimers using the murine air pouch model.
  
  
  METHODS
  Mice received appropriate negative and positive controls or G0-G3 PAMAM nanoparticles at 100 and 500 µg/ml into air pouches.
  
  
  METHODS
  Exudates were harvested after 3, 6, 24 and 48 h. Cell pellets and supernatants were used to determine the number of total leukocytes and neutrophils and to detect the production of several analytes by an antibody array approach, respectively. One-way analysis of variance was used for statistical analysis.
  
  
  RESULTS
  PAMAM dendrimers rapidly increased a leukocyte influx after 3 h, the vast majority of cells being neutrophils. This was also observed after 6 and 24 h, and resolution of inflammation was noted after 48 h. In general, the increased production of a greater number of analytes detected in the exudates after 6 h correlated with the number of dendrimer generations (G3 > G2 > G1 > G0).
  
  
  CONCLUSIONS
  PAMAM dendrimers devoid of any delivering molecules possess proinflammatory activities in vivo by themselves, probably via the production of different chemokines released by air pouch lining cells.
authors.affiliation: Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, Université du Québec, INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, H7V 1B7, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durocher
authors.affiliation: Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, Université du Québec, INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, H7V 1B7, Canada. denis.girard@iaf.inrs.ca.
authors.forename: Denis
authors.initials: D
authors.lastname: Girard
mesh_terms: D000818:Animals; D050091:Dendrimers / Q000494:pharmacology*; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007958:Leukocyte Count; D051379:Mice; D053758:Nanoparticles; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D018093:Gelatinases
keywords: Chemokines; Inflammation; Leukocytes; Murine air pouch; Neutrophils; Polyamidoamine (PAMAM) dendrimer