Galactosylated liposomes as carriers for targeting meso-2,3-dimercaptosuccinic acid to cadmium storage sites in cadmium exposed mice.

In this study an attempt has been made to examine the efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) using galactosylated liposomes as carriers for mobilization of cadmium from the body of mice preexposed to cadmium chloride (0.005 mmoles/kg intraperitoneally daily for 4 days). Cadmium-exposed mice after a rest period of 8 weeks were administered DMSA intravenously, two injections 15 micromoles/kg with an interval of 48 h, as free form of DMSA, or DMSA encapsulated in liposomes composed of phosphatidyl choline, cholesterol and phosphatidyl ethanolamine (7:2:1; PC-lip-DMSA) or in liposomes to which p-aminophenyl galactoside had been anchored (Gal-lip-DMSA). Excretion of cadmium through urine and feces was monitored for 5 days. Thereafter animals were sacrificed, liver, kidneys, spleen and isolated hepatocytes were analysed for cadmium, copper and zinc concentration. Efficacy for cadmium mobilization from the body was found to be in the order Gal-lip-DMSA>PC-lip-DMSA>DMSA. These results show that liposomes can be used as targeted carrier system for chelating agents safely and efficiently as compared to administration of free chelating agent.

[1]  M. Zern,et al.  Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents , 1998, Hepatology.

[2]  H. Loughrey,et al.  Targeting of doxorubicin loaded liposomes to T-cells via the transferrin receptor. , 1998, Biochemical Society transactions.

[3]  G. Banerjee,et al.  A Novel Peptide-Grafted Liposomal Delivery System Targeted to Macrophages , 1998, Antimicrobial Agents and Chemotherapy.

[4]  R. Srivastava,et al.  Efficacy of liposome encapsulated triethylenetetraamine hexaacetic acid (TTHA) against cadmium intoxication: role of lipid composition. , 1995, Industrial health.

[5]  M. Basu.  Liposomes in drug targeting. , 1994, Biotechnology & genetic engineering reviews.

[6]  R. Srivastava,et al.  Influence of size of liposomes in potentiating the efficacy of encapsulated triethylenetetramine-hexaacetic acid (TTHA) against cadmium intoxication. , 1993, Industrial health.

[7]  M. Jones,et al.  Monoisoamyl meso-2,3-dimercaptosuccinate: interaction with metallothionein-bound cadmium in vitro and evidence of active transport into renal and hepatic cells in vivo. , 1992, Research communications in chemical pathology and pharmacology.

[8]  L. M. Atkins,et al.  Cadmium mobilization in vivo by intraperitoneal or oral administration of monoalkyl esters of meso-2,3-dimercaptosuccinic acid in the mouse. , 1992, Pharmacology & toxicology.

[9]  G. Gregoriadis,et al.  A comparative study of free and liposome-entrapped diethylenetriaminepentaacetic acid used in the treatment of mice loaded with cadmium , 1992 .

[10]  R. Srivastava,et al.  Mobilization of cadmium by liposome-encapsulated meso-2,3-dimercaptosuccinic acid in pre-exposed mice. , 1991, Toxicology letters.

[11]  K. Brendel,et al.  Determination and metabolism of dithiol chelating agents. VII. Biliary excretion of dithiols and their interactions with cadmium and metallothionein. , 1990, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[12]  V. Weissig,et al.  Covalent coupling of sugars to liposomes. , 1989, Biochimica et biophysica acta.

[13]  Q. Fernaǹdo,et al.  Determination and metabolism of dithiol chelating agents. VIII. Metal complexes of meso-dimercaptosuccinic acid. , 1989, Toxicology and applied pharmacology.

[14]  M. Nordberg,et al.  On the role of metallothionein in cadmium induced renal toxicity. , 1987, Experientia. Supplementum.

[15]  J. Behari,et al.  Effect of thiol chelators on trace metal levels. , 1983, Research communications in chemical pathology and pharmacology.

[16]  C. Klaassen,et al.  Decreased effectiveness of chelation therapy with time after acute cadmium poisoning. , 1982, Toxicology and applied pharmacology.

[17]  P. Das,et al.  Targeting of liposomes towards different cell types of rat liver through the involvement of liposomal surface glycosides. , 1982, Archives of biochemistry and biophysics.

[18]  B. Fowler,et al.  Renal metabolism and toxicity of metallothionein. , 1982, Developments in toxicology and environmental science.

[19]  B. Bachhawat,et al.  Grafting of different glycosides on the surface of liposomes and its effect on the tissue distribution of 125I-labelled gamma-globulin encapsulated in liposomes. , 1980, Biochimica et biophysica acta.

[20]  D. Skilleter,et al.  Selective uptake of cadmium by the parenchyumal cells of liver. , 1980, The Biochemical journal.

[21]  B. Fowler,et al.  The renal toxicity of cadmium metallothionein: morphometric and X-ray microanalytical studies. , 1978, Toxicology and applied pharmacology.

[22]  R L Juliano,et al.  The effect of particle size and charge on the clearance rates of liposomes and liposome encapsulated drugs. , 1975, Biochemical and biophysical research communications.

[23]  R. Bloch,et al.  A rapid procedure for derivatizing agarose with a variety of carbohydrates: Its use for affinity chromatography of lectins , 1974, FEBS letters.

[24]  D. Friend,et al.  HIGH-YIELD PREPARATION OF ISOLATED RAT LIVER PARENCHYMAL CELLS , 1969, Journal of Cell Biology.

[25]  W. S. Singleton,et al.  Chromatographically homogeneous lecithin from egg phospholipids , 1965, Journal of the American Oil Chemists' Society.

[26]  F. Smith,et al.  COLORIMETRIC METHOD FOR DETER-MINATION OF SUGAR AND RELATED SUBSTANCE , 1956 .