Synthesis and evaluation of oxidation-responsive alginate-deferoxamine conjugates with increased stability and low toxicity
2016
Deferoxamine is commonly used for iron-overload related diseases, its drawbacks such as instability and toxicity, however, significantly limited its utility in clinic. To address these issues, oxidation-responsive alginate-deferoxamine (Alg-DFO) conjugates were synthesized and their structure was characterized. The metabolism studies shown the conjugation of alginate significantly increased the stability of the DFO, with half-life more than 10 times longer than that of the free DFO. Moreover, the conjugates could not only quickly respond to oxidative stimuli and degradation, suggesting their potential to be cleared from the body by responding to iron-overload associated oxidative environment to avoid its accumulation and safety concern, but also protect iron binding capacity of the attached DFO from oxidation. The degradation mechanism for oxidative-response was proposed. In addition, the conjugates shown lower cytotoxicity compared to the free DFO. Taken together, the Alg-DFO conjugates synthesized in this work has promise for treating iron-overload related conditions.
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