Targeting of diethylene triamine pentaacetic acid encapsulated in liposomes to rat liver: an effective strategy to prevent bone deposition and increase urine elimination of plutonium in rats.
OBJECTIVE
To modify the distribution of the chelating agent diethylene triamine pentaacetic acid (DTPA) by using a formulation approach with liposomes in order to match the in vivo distribution of plutonium (Pu) and, as a consequence, to improve actinide decorporation.


METHODS
DTPA was encapsulated in conventional and stealth liposomes. Their pharmacokinetics and ability to remove Pu were evaluated in rats 2 and 16 days after a single intravenous treatment given 2 h after contamination with colloidal Pu (239Pu phytate) or with soluble Pu (238Pu citrate).


RESULTS
Both formulations induced major pharmacokinetic modifications in rats, allowing an accumulation of [14C]-DTPA mainly in the liver and secondarily (for stealth liposomes) in bone and spleen. These modifications were associated with major increases in urine elimination and with a decrease in skeletal Pu deposition, depending of the nature of the Pu contaminant. After contamination by Pu phytate, conventional liposomes of DTPA (6 micromol kg(-1)) were as efficient as free DTPA (30 micromol kg(-1)) in maintaining the Pu content in the femur below 4.3% of the injected dose after 16 days, a 3.6-fold reduction compared with free DTPA (4 micromol kg(-1)) treatment or without treatment.


CONCLUSIONS
A formulation approach with liposomes appears to be a powerful tool to improve the efficiency of Pu chelating agents in vivo.
Phan
G
G
CEA, Service de Pharmacologie et d'Immunologie, Gif-sur-Yvette, France.
Ramounet-Le Gall
B
B
Manceau
J
J
Fanet
M
M
Benech
H
H
Fritsch
P
P
Fattal
E
E
Deverre
J R
JR
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D002614:Chelating Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D004369:Pentetic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011005:Plutonium / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
D002614:Chelating Agents; D008081:Liposomes; D011005:Plutonium; D004369:Pentetic Acid