caa a22 4500 477128459 CHVBK 20180405111656.0 cr unu---uuuuu 170330e19971101xx s 000 0 eng 10.1023/A:1012194721763 doi (NATIONALLICENCE)springer-10.1023/A:1012194721763 Activation of the Mononuclear Phagocyte System by Poloxamine 908: Its Implications for Targeted Drug Delivery [Elektronische Daten] [T. Armstrong, S. Moghimi, S. Davis, L. Illum] 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. Plenum Publishing Corporation, 1997 mononuclear phagocyte system nationallicence targeted drug delivery nationallicence nanoparticles nationallicence poloxamine 908 nationallicence Armstrong T. Department of Pharmaceutical Sciences, The University of Nottingham, University Park, NG7 2RD, Nottingham, UK aut Moghimi S. Department of Pharmaceutical Sciences, The University of Nottingham, University Park, NG7 2RD, Nottingham, UK aut Davis S. Department of Pharmaceutical Sciences, The University of Nottingham, University Park, NG7 2RD, Nottingham, UK aut Illum L. Department of Pharmaceutical Sciences, The University of Nottingham, University Park, NG7 2RD, Nottingham, UK aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1629-1633 0724-8741 14:11<1629 1997 14 11095 https://doi.org/10.1023/A:1012194721763 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012194721763 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Armstrong T. Department of Pharmaceutical Sciences, The University of Nottingham, University Park, NG7 2RD, Nottingham, UK aut NATIONALLICENCE 700 1- Moghimi S. Department of Pharmaceutical Sciences, The University of Nottingham, University Park, NG7 2RD, Nottingham, UK aut NATIONALLICENCE 700 1- Davis S. Department of Pharmaceutical Sciences, The University of Nottingham, University Park, NG7 2RD, Nottingham, UK aut NATIONALLICENCE 700 1- Illum L. Department of Pharmaceutical Sciences, The University of Nottingham, University Park, NG7 2RD, Nottingham, UK aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1629-1633 0724-8741 14:11<1629 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer