Wound Healing Society

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Transdermal Deferoxamine Significantly Enhances Healing Of Sickle Cell Ulcers
Melanie Rodrigues1, Clark A. Bonham1, Mohammed Inayathullah1, Jayakumar Rajadas1, George P. Yang1, Minniti P. Caterina2, Kalpna Gupta3, Michael T. Longaker1, Geoffrey C. Gurtner1.
1Stanford University School of Medicine, Stanford, CA, USA, 2Albert Einstein College of Medicine, Bronx, NY, USA, 3University of Minnesota, Minneapolis, MN, USA.

Background: Sickle cell disease (SCD) affects approximately 100,000 people in the United States and is associated with hemochromatosis. Roughly 2.5% of this patient population experience sickle cell ulcers (SCU), with the incidence increasing to 27% in patients in low income areas. SCUs form over the medial or lateral malleoli and are prone to infection and recidivism. Some ulcers can last up to 20 years or may never heal leading to pain, clubbed feet or amputations. There is no effective therapy for treating SCUs.
Methods: Deferoxamine is FDA-approved for the treatment of hemochromatosis and we have previously found deferoxamine to heal diabetic ulcers in murine models. Thus, we developed a clinical-grade transdermal deferoxamine delivery system (TDDS) for treating SCUs. TDDS was applied daily on excisional wounds in a murine model of SCD and compared to untreated wounds or wounds subcutaneously injected with deferoxamine. High performance liquid chromatography (HPLC) was used to test DFO release from the delivery system 24 hours following application on the wound. 50um wound sections were subjected to inductively coupled mass spectrometry to test for free iron.
Results: TDDS-treated wounds demonstrated significantly accelerated time to closure (p<0.05), reduction in wound size and improved wound remodeling as demonstrated by increased collagen deposition. HPLC confirmed release of deferoxamine from the TDDS into the dermis of both wounded skin and re-epithelialized skin. Plasma mass spectrometry demonstrated that TDDS chelated excessive free iron within the dermis as there was significantly lesser Fe2+ and Fe3+ (p<0.05) in this treatment group.
Conclusions: TDDS significantly enhances healing of ulcers by chelating excessive free-iron in a murine model of sickle cell disease. TDDS is currently being manufactured in an FDA-compliant and ISO-13485 facility to be rapidly translated for treating patients with sickle cell ulcers.


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