Decorporation and therapeutic efficacy of liposomal-DTPA against thorium-induced toxicity in the Wistar rat.
OBJECTIVE
This study examined the effect of liposomal encapsulation of (99m)Tc-labeled diethylenetriaminepentaacetic acid (metastable technetium labeled DTPA) on its organ distribution and therapeutic effect of optimized neutral liposomal-DTPA against thorium ((232)Th)-induced liver toxicity and its accumulation in rat animal model.


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


RESULTS
Neutral liposomes encapsulated with (99m)Tc-DTPA showed more uptake in liver, spleen and blood than with positively charged liposomal- and free- (99m)Tc-DTPA. Administration of (232)Th-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 (232)Th 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 (232)Th induced toxicity may be significantly improved by liposomal encapsulation of DTPA, a chelating agent.
Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.
Amit
A
Kumar
Pragya
P
Sharma
Manjoor
M
Ali
Badri Narain
BN
Pandey
Kaushala Prasad
KP
Mishra
D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D016284:Technetium Tc 99m Pentetate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013910:Thorium / Q000097:blood / Q000378:metabolism / Q000633:toxicity*
D002614:Chelating Agents; D008081:Liposomes; D013910:Thorium; D016284:Technetium Tc 99m Pentetate