Decorporation of Iron Metal Using Dialdehyde Cellulose-Deferoxamine Microcarrier
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Deferoxamine iron chelator has a limited therapeutic index due to rapid clearance from blood and possesses dose-limiting toxicity. Therefore, an intravenous deferoxamine delivery system based on dialdehyde cellulose (DAC) polymer was developed and its efficacy and toxicity were tested in iron-overloaded animals. The amino groups of deferoxamine were conjugated to free aldehyde moieties of dialdehyde cellulose via Schiff base reaction to form dialdehyde cellulose-deferoxamine (DAC-DFO) conjugate and characterized by Fourier transform infrared spectrophotometer, scanning electron microscope, and X-ray diffraction. The toxicity of prepared formulation was analyzed by XTT cell viability assay and LD50 study in mice. The change in serum iron levels, after intravenous administration of formulation, was observed in iron-overloaded rats. The DAC-DFO conjugate was tagged with Tc-99m to study the blood kinetics and observe change in blood circulation time. DAC-DFO conjugate was dispersible in water at concentration ∼75 mg/ml. In vitro cytotoxicity assay and LD50 study in mice indicated significantly enhanced safety of covalently bound deferoxamine (at >1000 mg/kg body weight compared to free drug at ∼270 mg/kg dose). A preliminary scintigraphy imaging and blood clearance study, with technetium-99m, indicated prolonged circulation of conjugated DFO in rabbit blood. A single dose of formulation injected into iron overloaded animals was found to maintain the normal serum iron levels until 10 days. The polymeric conjugate was effective in maintaining normal serum iron levels until 10 days at a dose of 100 mg/kg body weight.
KEY WORDSdeferoxamine dialdehyde cellulose iron chelation iron decorporation iron overload
The authors gratefully acknowledge the Department of Science and Technology (DST), India, for providing funds to carry out the research work. The authors are also thankful to Dr. R. P. Tripathi, Director, Institute of Nuclear Medicine & Allied Sciences (INMAS), DRDO, Delhi, India, for providing animal facility and scintigraphy studies.
COMPLIANCE WITH ETHICAL STANDARDS
The authors are responsible for the content and writing of the paper. The study protocol was reviewed and approved by the Institutional Animal Ethics Committee of INMAS.
Conflict of Interest
The authors declare that there are no competing interests.