title: Decorporation of Iron Metal Using Dialdehyde Cellulose-Deferoxamine Microcarrier.
abstract: 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 LD50study 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.
authors.affiliation: Center for Biomedical Engineering, Indian Institute of Technology, Delhi, 110016, India. priyanka.tgi@gmail.com.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Tyagi
authors.affiliation: Department of Nuclear Medicine, Institute of Nuclear Medicine & Allied Sciences (INMAS), DRDO, Delhi, 110054, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Center for Biomedical Engineering, Indian Institute of Technology, Delhi, 110016, India.
authors.forename: Dikshi
authors.initials: D
authors.lastname: Gupta
authors.affiliation: Center for Biomedical Engineering, Indian Institute of Technology, Delhi, 110016, India.
authors.forename: Harpal
authors.initials: H
authors.lastname: Singh
mesh_terms: D000818:Animals; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003676:Deferoxamine / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D007501:Iron / Q000097:blood / Q000378:metabolism*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy; D007700:Kinetics; D008297:Male; D051379:Mice; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004337:Drug Carriers; D002482:Cellulose; C058684:2,3-dialdehydocellulose; D007501:Iron; D003676:Deferoxamine
keywords: deferoxamine; dialdehyde cellulose; iron chelation; iron decorporation; iron overload