title: Re-establishing the long circulatory behaviour of poloxamine-coated particles after repeated intravenous administration: applications in cancer drug delivery and imaging.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nottingham, UK. s.m.moghimi@brighton.ac.uk
authors.forename: S M
authors.initials: SM
authors.lastname: Moghimi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood*; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers; D005029:Ethylenediamines / Q000008:administration & dosage*; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D004337:Drug Carriers; D005029:Ethylenediamines; C012571:tetronic 701; D011092:Polyethylene Glycols