SBIR-STTR Award

In chemical and biological systems, iron is both ubiquitous and highly reactive. In a variety of circumstances, there is great need for new approaches to the removal of iron or the control of its reactivity. Biomedical Frontiers has produced a series of high molecular weight iron chelators based on derivation of a number of substrates with deferoxamine B. This chelator has an extremely high affinity for iron and is very selective (i.e., has relatively low affinity for other polyvalent cations aside from aluminum). Adducts have been produced between deferoxamine B and both soluble polymers and solid matrices.The present proposal relates to maximization of derivation procedures, definition of appropriate conditions of modification, and determination of the physical characteristics of the derived materials. The high molecular weight iron chelators produced as a result of this work have a number of potential (Phase II) applications. These include: (1) the selective and quantitative removal of iron from solutions, (2) a simple and rapid procedure for serum iron determination, (3) more effective iron chelation therapy, and (4) the control of bacterial infections that are promoted by free iron.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

In the past 40 years, biochemical researchers have investigated the deleterious effects of free or reactive iron, and recent experiments have examined its significance in biology and medicine. The results suggest that iron, in conjunction with oxygen radicals, plays an important role in a number of different clinical situations, including myocardial infarct, shock, stroke, surgery, and trauma. These data imply that the chelation or inactivation of iron may have considerable therapeutic potential.The only iron chelator currently approved for clinical use, deferrioxamine, has therapeutic limitations because of its short circulatory halflife and toxicity. An assortment of modified iron chelators has been developed by attaching deferrioxamine to either polysaccharide or peptide polymers, thereby increasing its molecular weight. These high-molecular-weight chelators manifest decreased toxicity and increased circulatory retention times, and they may have significant therapeutic potential.The goal of this Phase II proposal is to advance the development of a family of therapeutics that can be utilized when iron-dependent pathophysiology is suspected in the etiology of a clinical condition. The iron chelation efficiency of these novel compounds will be assessed, and their physical and biochemical properties will be characterized. The production of these chelators will be increased, and their therapeutic efficacy will be assessed in animal models in several clinical conditions.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)