Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Topical Deferoxamine Penetrates the Dermis and Increases Cutaneous Vascularity: The Development of a Topical Therapy for Radiation Soft Tissue Injury
Kasandra R. Hanna, MD, Alexander F. Mericli, MD, Patrick S. Cottler, PhD, Lisa S. Salopek, LVT, Yalin Wang, PhD, Jessica S. Wang, BS, Madeline M. Stovall, BA, George T. Rodeheaver, PhD, Kant Y. Lin, MD.
University of Virginia, Charlottesville, VA, USA.

PURPOSE: Radiation therapy is necessary in the treatment of breast cancer, however it is associated with an increased complications in both autologous and implant-based reconstruction. Deferoxamine (DFX) is an FDA approved iron chelator, which has been shown to promote angiogenesis and act as a free-radical scavenger. Our group has previously demonstrated the ability of subcutaneously delivered DFX in an irradiated TRAM flap model to improve vascularity and skin elasticity. The purpose of the present work is to develop a topical DFX with the intent to mitigate radiation induced soft tissue damage.
METHODS: Fourteen immunocompetent hairless rats were randomized to three groups: six were treated with a topical preparation of reconstituted DFX with a dermal penetrance enhancer (DPE), six were treated with a DPE alone (control), and two were treated with reconstituted DFX alone. Three 3 mm punch biopsies were procured from treated skin along the dorsum of the rat. Biopsies were taken in the DFX treated groups after 8 applications, 12 days after treatment began and after 3 applications, 5 days after treatment began, in the control group. In order to determine whether the DFX had penetrated the epidermis, we examined tissue from each rat with a fluorescent confocal microscope. DFX causes the accumulation of a naturally occurring fluorophore, protoporphyrin IX (PPIX). When excited at 405 nm, it emits fluorescence at 630 nm, which appears red. PPIX fluorescence can then be used as a surrogate marker of active DFX. Fluorescence was digitally quantified by pixel count after excluding artifact from red blood cells which contain high levels of PPIX regardless of DFX treatment (figure 1). Vascularity was evaluated by vessel count per high-powered-field after staining tissue with hematoxylin and eosin.
RESULTS: Rat skin treated with DFX alone showed the greatest number of mean red pixels (80. 4 ± 6.9), followed by DFX with a DPE (70.9 ± 8.7), and lastly, the DPE alone control group (65.3 ± 6.5), p= 0.001 (figure 2). Regarding vascularity, DFX alone showed the greatest number of vessels per high powered field (6.2 ± 2.6), followed by DFX with DPE (4.8 ± 3.4), and lastly DPE alone (3.4 ± 2.1), p=0.002 (figure 3).
CONCLUSIONS: This preliminary work suggests the ability of topically delivered DFX to penetrate the epidermis, the principle challenge in developing a topical drug. Furthermore, topical administration of DFX is associated with increased cutaneous vascularity as measured by histologic analysis. This is the first step in the process to test the ability of topical DFX to mitigate radiation induced soft tissue damage. Our next step will be to determine the ability of the topical DFX to promote angiogenesis, decrease scar, and promote elasticity in a small animal model of implant based breast reconstruction.


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