Re-establishing the long circulatory behaviour of poloxamine-coated particles after repeated intravenous administration: applications in cancer drug delivery and imaging.

In accordance with earlier observations, a single intravenous injection of long circulatory poloxamine-908-coated polystyrene particles to rats dramatically affected the circulation half-life and body distribution of a second dose when administered 10 days later. Both liver and spleen macrophages recognised and cleared from the blood the majority of the second dose of poloxamine-908-coated particles. The second dose of poloxamine-908-coated particles, however, regained their long circulatory behaviour when administered 1-3 h after a bolus intravenous injection of 30 mg free poloxamine-908 or poloxamer-407 (in saline)/150 g body weight. When the interval between free copolymer and particle administration was increased to 24 h then macrophage-rich organs were able to extract poloxamine-coated beads from the blood. In contrast to poloxamine-908 and poloxamer-407, prior administration of poloxamer-188 and polyethyleneglycol-20000 also failed to restore the long circulatory behaviour of the second dose of poloxamine-908-coated particles. These observations are of interest in experimental drug delivery, particularly in experimental cancer therapy (diagnostic imaging and drug delivery), involving multiple injections of poloxamine-based long circulating nanosized vehicles.