Transdermal Deferoxamine Enhances Wound Healing In Aged Mice
Clark A. Bonham, Melanie Rodrigues, Artem Trotsyuk, Zachary Stern-Buchbinder, Mohammed Inayathullah, Jayakumar Rajadas, Geoffrey C. Gurtner.
Stanford, Stanford, CA, USA.
Background: There are currently 46.2 million people in the United States over 65 years old. By 2060, this number is expected to rise to 98 million. Chronic wounds, especially pressure ulcers, disproportionately affect elderly individuals causing substantial morbidity and mortality to the patient, and expense to the healthcare system. There are no effective therapies for treating chronic wounds in aged patients and most clinical trials exclude the elderly due to poorly defined outcomes and variables. We have previously shown that defective hypoxia signaling through destabilization of the master hypoxia-inducible factor 1α (HIF-1α) underlies neovascular and wound healing impairments in both aging and diabetes.
Methods: To stabilize HIF-1α, we developed a transdermal delivery system of the FDA-approved small molecule deferoxamine (DFO) and tested release of drug into the human dermis using a Franz cell set-up. For the first time we applied transdermal DFO on excisional wounds in aged mice and compared rate of healing to untreated wounds in both young and aged mice. Wound lysates were isolated and subjected to Western blotting for HIF-1α. Histological sections were stained with CD31 for new vessel formation.
Results: In vitro, transdermal DFO was consistently released into the dermis in the Franz cell setup but did not penetrate beyond the dermis. When applied on aged excisional wounds, we observed significantly accelerated wound closure (*p<0.05) through stabilization of HIF-1α compared to the untreated groups. There were significant improvements in neovascularization in the transdermal DFO treatment group confirmed by CD31 staining (*p<0.05).
Conclusions: Transdermal DFO enhances impaired wound healing in aged mice. This drug delivery system can be scaled in an FDA-compliant facility and rapidly translated to the clinic for treating both chronic wounds and pressure ulcers in aged patients.
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