title: Activation of the mononuclear phagocyte system by poloxamine 908: its implications for targeted drug delivery.
abstract: OBJECTIVE
  To investigate the effect of poloxamine 908 on the MPS activity and the importance of its mode of presentation to the immune system.
  
  
  METHODS
  Solutions of endotoxin free poloxamine 908 were injected daily intravenously to rats, and the effect on the degree of sequestration by the liver of I125 labelled, poloxamine 908-coated 60 nm polystyrene particles was investigated by studying effect of dosing regimen(s) and assessment of opsonic activity.
  
  
  RESULTS
  After 3 or 4 days repeated dosing with poloxamine 908 (0.7 mg) in solution, the poloxamine 908-coated polystyrene particles (60 nm) were rapidly cleared from the circulation. The increase sequestration of the particles by the liver lasted for more than 7 days after last dosing with the poloxamine 908 solution. In subsequent studies, it was found that a single dose of poloxamine 908 (0.7 mg) in solution was sufficient to activate the MPS 4 days after the injection. The increased uptake was found not be mediated by a serum component, nor was it due to proliferation of the Kupffer cells in the liver.
  
  
  CONCLUSIONS
  The results provide evidence that a solution of endotoxin-free poloxamine 908 activates the MPS so that 4 days after injection otherwise long-term circulating poloxamine 908-coated particles are sequestered by the liver. This finding has implications for use of such coated systems in therapeutic situations.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nottingham, UK.
authors.forename: T I
authors.initials: TI
authors.lastname: Armstrong
authors.forename: S M
authors.initials: SM
authors.lastname: Moghimi
authors.forename: S S
authors.initials: SS
authors.lastname: Davis
authors.forename: L
authors.initials: L
authors.lastname: Illum
mesh_terms: D000818:Animals; D001682:Biological Availability; D004334:Drug Administration Schedule; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005029:Ethylenediamines / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D009000:Monocytes / Q000187:drug effects*; D009895:Opsonin Proteins / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D005029:Ethylenediamines; D009895:Opsonin Proteins; C012571:tetronic 701; D011092:Polyethylene Glycols