Hydroxamic Acid-Containing Hydrogels for Nonabsorbed Iron Chelation Therapy: Synthesis, Characterization, and Biological Evaluation

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• 作者：Steven C. Polomoscanik ; C. Pat Cannon ; Thomas X. Neenan ; S. Randall Holmes-Farley ; W. Harry Mandeville ; and Pradeep K. Dhal
• 刊名：Biomacromolecules
• 出版年：2005
• 出版时间：November 2005
• 年：2005
• 卷：6
• 期：6
• 页码：2946 - 2953
• 全文大小：76K
• 年卷期：v.6,no.6(November 2005)
• ISSN：1526-4602

文摘

Iron overload is a severe clinical condition and can be largely prevented by the use of iron-specific chelatingagents. A successful iron chelator needs to be orally active, nontoxic, and selective. In this study, hydrogelscontaining pendant hydroxamic acid groups have been synthesized as potential nonabsorbed chelators foriron in the gastrointestinal tract. The synthetic method employed to introduce hydroxamic acid groups topolymer chains involved reaction of polymer gels based on N-acryloxysuccinimide, acryloyl chloride, and(2-hydroxyethyl)acrylate monomers with hydroxylamine. These hydroxamic acid-functionalized polymergels swell favorably in water and effectively sequester iron. In vitro iron-binding properties of these hydrogelswere evaluated from their binding isotherms by use of iron(II) alone and in the presence of other competingmetal ions. These polymers bind iron over a broad pH range. The iron-binding properties of the polymerswere found to depend on the concentration of hydroxamate groups on polymer chains. The in vivo iron-binding efficacy of the polymers was evaluated in rat as the animal model. The polymers prevented anincrease in serum hemoglobin and hematocrit levels in the animals, thus suggesting the prevention of systemicabsorption of dietary iron from the gastrointestinal tract. The animals also maintained normal body weightduring the treatment period, indicating the absence of any apparent toxicity associated with these polymers.