Intracellular Plutonium: Removal by Liposome-Encapsulated Chelating Agent

Abstract

Chelating agents, such as ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) were successfully encapsulated within lipid spherules (that is, liposomes). Encapsutlated [(14)C]EDTA, given intravenously to mice, was retained longer in tissues that nonencapsulated [(14)C]EDTA. Encapsulated DTPA, given to mice 3 days after pluttonium injection, removed an additional fraction of plutonium in the liver, presumably intracellular, not available to nonencapslulated DTPA. It also further increased urinary excretion of plutonium. Introduction of chelating agents into cells by liposomal encapsulation is a promising new approach to the treatment of metal poisoning

Liposomes containing chelating agents. Cellular penetration and a possible mechanism of metal removal.

“…The tissue disposition of liposome-encapsulated EDTA, however, is strikingly different from that of nonencapsulated EDTA (9). The highest therapeutic doses of chelating agents used in our studies (7,8) 1 were 100 mg (EDTA or DTPA) per kg, and under such experimental conditions no vacuologenesis was observed in liver, lungs, and spleen, the tissues we have examined so far.…”

“…By combining results of the kinetic studies and the present morphological studies, we can reasonably assume that the chelating agent encapsulated within liposomes has been successfully transported across the cellular membrane. The injection into mice of the chelating agent DTPA in liposome-encapsulated form has been shown to remove a fraction of the metal plutonium from the liver that was not available to nonencapsulated DTPA therapy (8). 1 This fraction of the metal is presumably localized inside the liver cells.…”

“…Liposomes containing DTPA, when injected into mice, are readily taken up by tissue cells. These liposomes have been successful in removing various intracellularly deposited toxic metals from mice (e.g., plutonium, lead, and inorganic mercury) (7,8)?…”

Penetration of target areas in the rat by liposome‐associated bleomycin, glucose oxidase and insulin

“…A wide variety of liposome-associated enzymes, drugs and other agents has been successfully applied in model systems for enzyme replacement therapy [2][3][4], cancer chemotherapy [5][6][7], heavy metal detoxification [8], prevention of viral infections [9] and also as immunological adjuvants [10,11 ], interferon inducers [12] and diagnostic agents [13]. In addition, liposomes have been used for the introduction into cells of agents which, normally, have no intracellular access [ 14,15 ].…”

Liposomology: delivering the message

“…Thus, by 1973, a number of researchers worldwide started to use liposomes in drug delivery, for instance metal detoxification (Rahman et al 1973), the effect of vesicle size on vesicle clearance from the blood circulation (Juliano and Stamp 1975), and the interaction of liposomes with cells (Papahadjopoulos et al 1974, Scherphof et al 1975. Liposomology was on the road to becoming a promising new field with great potential in the treatment of disease including certain forms of cancer (Gabizon and Barenholz 1988 ), mannosidosis (Patel and Ryman 1974), antimicrobial therapy, principally against fungal infections (Lopez-Berestein et al 1987), the control of liposomal vesicle stability and clearance from the blood circulation (Gregoriadis and Senior, 1980), and in the form of immunological adjuvants, in a malaria vaccine (Alving et al 1986).…”