TY - JOUR
T1 - Activation of the mononuclear phagocyte system by poloxamine 908
T2 - Its implications for targeted drug delivery
AU - Armstrong, T. I.
AU - Moghimi, S. M.
AU - Davis, S. S.
AU - Illum, L.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1997
Y1 - 1997
N2 - 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 increased 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.
AB - 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 increased 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.
KW - Mononuclear phagocyte system
KW - Nanoparticle
KW - Poloxamine 908
KW - Targeted drug delivery
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U2 - 10.1023/A:1012194721763
DO - 10.1023/A:1012194721763
M3 - Article
C2 - 9434285
AN - SCOPUS:0031442497
SN - 0724-8741
VL - 14
SP - 1629
EP - 1633
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 11
ER -