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

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 and 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 µmol kg⁻¹) were as efficient as free DTPA (30 µmol 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 µmol 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.