Evaluation of calcium di-sodium EDTA intramuscular injection using gamma scintigraphy against heavy metal poisoning

Full text: Heavy metals become toxic when they are not metabolized by the body and accumulate in soft tissues. These metals may enter the body through food, water, air or absorption through skin when an individual is exposed to areas with high heavy metal content such as agriculture, pharmaceutical manufacturing, paint and heavy metal industries or residential settings. Majority of population commonly get affected by heavy metal poisoning. Heavy metal poisoning is more likely to result through inhalation or ingestion route. Aim of the present study is to provide an easy, effective and controlled chelating therapy against heavy metal using Ca-disodium EDTA intramuscular injection. Ca-disodium-EDTA and Sesame oil were procured from Merck, India and Sigma Aldrich, USA respectively. Ca-Na2EDTA radiolabeling with 99mTc-pertechnetate was standardized using stannous ions as reducing agent. The hypothesis of present work is to maintain effective concentration of chelating agent in blood for prolong time period. To test this hypothesis, we studied 1% Ca-Na2EDTA blood bioavailability after intramuscular depot administration in new zealand white rabbit. The optimized radiolabeled intramuscular formulation was evaluated for its dissolution and permeation studies in isotonic buffer solution were envisaged through radiometry. Sub-acute toxicity studies were performed after a single dose intramuscular administration of 1% Ca-Na2EDTA in Sprague Dawley rats. Radiolabeled Ca-disodium-EDTA (>95% labeled) was found to be fairly stable up to 24 h in physiological solution (Serum) as well as in normal saline with negligible degradation of 2.5% and 5.0% respectively, thereby indicating high stability of radiolabeled product. In-vitro data indicates that control release pattern (Cmax 24 hrs) with effective concentration up to seven days. 99mTc-CaNa2EDTA retention at depot site was estimated up to 3 days by scintigraphy. Subacute toxicity studies done by histopathological investigation of rat muscle and no significant alterations were detected in pathological examinations of the tissues in comparison to control group animals. Conclusively this studies indicates that Ca-disodium EDTA i.e. injection is stable, safe and may be effective in chelation of various heavy metal on single dose i.m. depot