Decorporation and therapeutic efficacy of liposomal-DTPA against thorium-induced toxicity in the Wistar rat

作者：Kumar Amit; Sharma Pragya; Ali Manjoor; Pandey Badri Narain; Mishra Kaushala Prasad^*

来源：International Journal of Radiation Biology, 2012, 88(3): 223-229.

DOI：10.3109/09553002.2011.634883

• Thorium
• liposomes
• decorporation
• liver toxicity

Purpose: This study examined the effect of liposomal encapsulation of Tc-99m-labeled diethylenetriaminepentaacetic acid (metastable technetium labeled DTPA) on its organ distribution and therapeutic effect of optimized neutral liposomal-DTPA against thorium (Th-232)-induced liver toxicity and its accumulation in rat animal model.
Materials and methods: Tc-99m-DTPA was encapsulated in neutral (dipalmitoylphosphatidylcholine:cholesterol) and positively (dipalmitoylphosphatidylcholine: cholesterol: stearylamine) charged liposomes using thin film hydration method. Comparative efficacy of liposomal and free DTPA (11.2 mg/kg) was examined in terms of its effect on Th-232 accumulation and subsequent toxicity in the liver and blood of rat administered with Th-232-nitrate (600 mu g/kg). Organ distribution of free or liposomal Tc-99m-DTPA was determined by solid scintillation counting and Th-232 accumulation by Inductively Coupled Plasma-Atomic Emission Spectroscopy.
Results: Neutral liposomes encapsulated with Tc-99m-DTPA showed more uptake in liver, spleen and blood than with positively charged liposomal-and free- Tc-99m-DTPA. Administration of Th-232-nitrate to rat significantly increased the levels of liver toxicity markers and of oxidative injury, which were found to be restored more significantly by neutral liposomal-DTPA than free-DTPA. The accumulation of Th-232 in liver and blood of contaminated mice was found to be decreased more significantly by neutral liposomal-DTPA than by free-DTPA.
Conclusions: Decorporation and consequent mitigation of Th-232 induced toxicity may be significantly improved by liposomal encapsulation of DTPA, a chelating agent.

• 出版日期2012-3