A COMPARATIVE-STUDY OF FREE AND LIPOSOME-ENTRAPPED DIETHYLENETRIAMINEPENTAACETIC ACID USED IN THE TREATMENT OF MICE LOADED WITH CADMIUM

Liposomes composed of equimolar egg phosphatidylcholine and cholesterol and containing diethylenetriaminepentaacctic acid (DTPA) were prepared by the dehydration-rehydration procedure. Such liposomes retained most of their DTPA content during either storage (for up to 30 days) or incubation in the presence of blood plasma at 37-degrees-C. In vivo experiments with mice pretreated with CdCl2 or phosphate-buffered saline (PBS) and subsequently injected intravenously with DTPA-containing liposomes or free DTPA revealed that: (a) liposomal DTPA was cleared from the circulation at a slower rate than the free chelator, (b) liposomal DTPA in Cd-treated mice had a more rapid rate of clearance than in PBS-treated mice; (c) whereas levels of DTPA injected in the free form were practically nil in the liver and spleen of both groups of mice at 24 h, those of liposomal DTPA were considerably higher (15 and 6% in the two tissues, respectively) in normal mice and much higher in cadmium treated mice (6% and 10%). In separate experiments, the cadmium-chelating action of free and liposomal DTPA injected intravenously was investigated in mice pre treated with CdCl2. The results showed that although there was no difference in the extent of cadmium reduction in the tissues between the two forms of DTPA, blood levels of the metal were lower for most of the 72 h period after treatment and its urinary excretion higher (during the first 24 h period) in mice injected with the liposomal chelator. It is suggested that treatment of cadmium poisoning with liposomal DTPA would present the kidneys with a lower concentration of cadmium for clearance into the urine over time thereby potentially reducing the nephrotoxicity of the metal.