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Activation of the mononuclear phagocyte system by poloxamine 908: its implications for targeted drug delivery
T I Armstrong1, S M Moghimi, S S Davis
1Department of Pharmaceutical Sciences, University of Nottingham, UK.
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.
Insights
Poloxamine 908 solution activates the mononuclear phagocyte system (MPS) in rats, leading to rapid clearance of coated particles by the liver. This immune system activation occurs even after a single dose, with implications for therapeutic applications.
Area of Science:
- Immunology
- Nanotechnology
- Pharmacology
Background:
- The mononuclear phagocyte system (MPS) plays a crucial role in immune surveillance and clearance of foreign particles.
- Poloxamine 908 is a non-ionic surfactant with potential applications in drug delivery and biomaterials.
- Understanding how poloxamine 908 interacts with the MPS is essential for its safe and effective use.
Purpose of the Study:
- To investigate the impact of poloxamine 908 on MPS activity.
- To determine the influence of poloxamine 908's presentation method on immune system engagement.
- To assess the potential of poloxamine 908 as an immune modulator.
Main Methods:
- Endotoxin-free poloxamine 908 solutions were administered intravenously to rats.
- The effect on the liver's sequestration of poloxamine 908-coated polystyrene particles was evaluated.
- Dosing regimens and opsonic activity were assessed to understand MPS activation.
Main Results:
- Repeated dosing of poloxamine 908 led to rapid clearance of coated particles by the liver within 3-4 days.
- This enhanced sequestration persisted for over 7 days post-dosing.
- A single dose of poloxamine 908 was sufficient to activate the MPS, with peak effect at 4 days.
Conclusions:
- Endotoxin-free poloxamine 908 solution effectively activates the MPS in rats.
- Activated MPS leads to efficient hepatic sequestration of poloxamine 908-coated particles.
- These findings suggest potential therapeutic applications for poloxamine 908-modified systems.