Activation of the Mononuclear Phagocyte System by Poloxamine 908: Its Implications for Targeted Drug Delivery

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 1998 Jan 22

PMID 9434285

Citations 1

Authors

T I Armstrong

S M Moghimi

S S Davis

L Illum

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Pharmacokinetics and urinary excretion of amikacin in low-clearance unilamellar liposomes after a single or repeated intravenous administration in the rhesus monkey.

Fielding R, Moon-McDermott L, LEWIS R, Horner M Antimicrob Agents Chemother. 1999; 43(3):503-9.

PMID: 10049258 PMC: 89151. DOI: 10.1128/AAC.43.3.503.

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