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.
Int J Radiat Biol
; 80(6): 413-22, 2004 Jun.
Article
em En
| MEDLINE
| ID: mdl-15362694
ABSTRACT
PURPOSE:
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. MATERIALS ANDMETHODS:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osso e Ossos
/
Quelantes
/
Plutônio
/
Ácido Pentético
/
Fígado
Limite:
Animals
Idioma:
En
Revista:
Int J Radiat Biol
Assunto da revista:
RADIOLOGIA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
França