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  • Iron Chelation In Wounds

    From ironjustice@21:1/5 to All on Tue Oct 2 08:41:21 2018
    Iron Chelation with Transdermal Deferoxamine Accelerates Healing of Murine Sickle Cell Ulcers
    Melanie Rodrigues, Clark A. Bonham, Caterina P. Minniti, Kalpna Gupta, Michael T. Longaker, and Geoffrey C. Gurtner
    Published Online:18 Jun 2018 https://doi.org/10.1089/wound.2018.0789
    Advances in Wound Care
    Discovery Express
    Abstract
    Objective: Sickle cell ulcers (SCUs) are a devastating comorbidity affecting patients with sickle cell disease (SCD). SCUs form over the medial or lateral malleoli of the lower extremity, are slow to heal, and prone to recidivism. Some SCUs may never
    heal, leading to chronic pain and foot deformities. There is no specific and effective therapy for SCUs. Systemic deferoxamine (DFO) has been demonstrated to prevent some of the sequelae of SCD by chelating iron. In this study, we tested the ability of
    DFO delivered via a transdermal delivery system (DFO-TDDS) to accelerate healing in a murine model of SCU.

    Approach: Excisional wounds were created in a transgenic murine model of SCD expressing >99% human sickle hemoglobin, and healing rates were compared with wounds in wild-type mice. Next, excisional wounds in SCD mice were treated with DFO-TDDS, DFO
    injection, or left untreated. Wound closure rates, histology, and iron in the healed wounds were analyzed.

    Results: Wounds in SCD mice healed significantly slower than wild-type mice (***p < 0.001). DFO-TDDS-treated wounds demonstrated significantly accelerated time to closure, reduced size, and improved wound remodeling compared with untreated wounds (***
    p < 0.001) and DFO injection treatment (*p < 0.05). DFO released from the TDDS into wounds resulted in chelation of excessive dermal-free iron.

    Innovation: DFO-TDDS is a novel therapeutic that is effective in healing wounds in sickle cell mice.

    Conclusion: DFO-TDDS significantly accelerates healing of murine SCUs by chelation of excessive free iron and is currently manufactured in an FDA-compliant facility to be translated for treating human SCUs.

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