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

Abstract

Purpose: This study examined the effect of liposomal encapsulation of ^99mTc-labeled diethylenetriaminepentaacetic acid (metastable technetium labeled DTPA) on its organ distribution and therapeutic effect of optimized neutral liposomal-DTPA against thorium (²³²Th)-induced liver toxicity and its accumulation in rat animal model.

Materials and methods: ^99mTc-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 ²³²Th accumulation and subsequent toxicity in the liver and blood of rat administered with ²³²Th-nitrate (600 μg/kg). Organ distribution of free or liposomal ^99mTc-DTPA was determined by solid scintillation counting and ²³²Th accumulation by Inductively Coupled Plasma-Atomic Emission Spectroscopy.

Results: Neutral liposomes encapsulated with ^99mTc-DTPA showed more uptake in liver, spleen and blood than with positively charged liposomal- and free- ^99mTc-DTPA. Administration of ²³²Th-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 ²³²Th 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 ²³²Th induced toxicity may be significantly improved by liposomal encapsulation of DTPA, a chelating agent.

Keywords::

• Thorium
• liposomes
• decorporation
• liver toxicity

Acknowledgements

The authors thank Mr Sumit Kumar, Dr P. N. Pathak and Dr V. K. Manchanda, Radiochemistry Division, BARC for providing thorium nitrate. The authors would also like to acknowledge the help of the late Mr S. Shah for ICP-AES and Mrs Hansa Yadav for her technical assistance.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.