Document Detail

Activation of the mononuclear phagocyte system by poloxamine 908: its implications for targeted drug delivery.
MedLine Citation:
PMID:  9434285     Owner:  NLM     Status:  MEDLINE    
PURPOSE: 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.
T I Armstrong; S M Moghimi; S S Davis; L Illum
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmaceutical research     Volume:  14     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1998-02-19     Completed Date:  1998-02-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1629-33     Citation Subset:  IM    
Department of Pharmaceutical Sciences, University of Nottingham, UK.
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MeSH Terms
Biological Availability
Drug Administration Schedule
Drug Carriers / administration & dosage*,  pharmacokinetics*
Ethylenediamines / administration & dosage*,  analysis,  pharmacokinetics*
Macrophage Activation / drug effects*
Monocytes / drug effects*
Opsonin Proteins / metabolism
Polyethylene Glycols / administration & dosage*,  analysis,  pharmacokinetics*
Rats, Wistar
Tissue Distribution
Reg. No./Substance:
0/Drug Carriers; 0/Ethylenediamines; 0/Opsonin Proteins; 0/Polyethylene Glycols; 11111-34-5/tetronic 701

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