Pharmacokinetics of DTPA entrapped in conventional and long-circulating liposomes of different size for plutonium decorporation.
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.
Phan
Guillaume
G
CEA, Service de Pharmacologie et d'Immunologie, Gif-sur-Yvette, France.
Herbet
Amaury
A
Cholet
Sophie
S
Benech
Henri
H
Deverre
Jean-Robert
JR
Fattal
Elias
E
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
D002250:Carbon Radioisotopes; D002614:Chelating Agents; D008081:Liposomes; D011092:Polyethylene Glycols; D011005:Plutonium; D004369:Pentetic Acid