title: Pharmacokinetics of DTPA entrapped in conventional and long-circulating liposomes of different size for plutonium decorporation.
abstract: The aim of the present study was to develop an efficient DTPA liposome formulation designed for plutonium decorporation. DTPA was encapsulated in conventional (CL) and polyethylene glycol-coated stealth liposomes (SL) prepared by extrusion followed by the freeze-thawing method and sizing from around 100 to 800 nm. DTPA encapsulation percentages were approximately 30% in CL of any size but dropped from 48% to 7% as the diameter of SL was reduced. The pharmacokinetics of [(14)C]-DTPA encapsulated in large and small vesicles was evaluated in rats after a single intravenous administration. Both liposomal composition and size reduction had a significant impact on pharmacokinetic parameters, inducing a marked increased in exposure of the body to DTPA and its delayed excretion. DTPA distribution was moderate in liver but enhanced in spleen and bone and was dose-dependent, especially when SL of 100 nm were given. In conclusion, small and stealth(R) vesicles have interesting properties in delivering DTPA to contaminated tissues.
authors.affiliation: CEA, Service de Pharmacologie et d'Immunologie, Gif-sur-Yvette, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Phan
authors.forename: Amaury
authors.initials: A
authors.lastname: Herbet
authors.forename: Sophie
authors.initials: S
authors.lastname: Cholet
authors.forename: Henri
authors.initials: H
authors.lastname: Benech
authors.forename: Jean-Robert
authors.initials: JR
authors.lastname: Deverre
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D002614:Chelating Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D010316:Particle Size; D004369:Pentetic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011005:Plutonium / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D002614:Chelating Agents; D008081:Liposomes; D011092:Polyethylene Glycols; D011005:Plutonium; D004369:Pentetic Acid