Deferoxamine Transdermal Application Decreases Fibrosis And Improves Elasticity In Irradiated Porcine Skin
Darren B. Abbas, M.D., Christopher V. Lavin, MS, Evan J. Fahy, MB Bch BAO, MCh, Michelle Griffin, MBChB, Ph.D, Nestor M. Diaz Deleon, BS, Nicholas Guardino, BS, Hendrik Lintel, BS, Geoffrey C. Gurtner, MD, Michael T. Longaker, MD, MBA, Derrick C. Wan, MD.
Stanford University, Stanford, CA, USA.
Introduction: Radiation therapy is notorious for its effectiveness in oncologic treatment but its devastating side effects to the surrounding soft tissue. We have previously demonstrated the efficacy of a transdermal drug delivery system (TDDS) to deliver deferoxamine (DFO) cutaneously to irradiated porcine skin safely without any systemic effects. With this study, we aim to demonstrate the beneficial effects of deferoxamine on irradiated porcine skin. Methods and Materials: Six red Duroc pigs (three months old) were irradiated with a single fraction of 30 Gy bilaterally. The pigs were allowed to recover for 12 weeks to allow chronic fibrosis to develop. The pigs were then divided into 4 different treatment conditions: normal, non-irradiated skin, irradiated skin with no patch (IR control), vehicle patch, and 1.0mg DFO TDDS patch (A). The pigs were treated with daily patch changes for 4 weeks and harvested immediately following the 4 weeks of treatment of after waiting another 4 weeks post-treatment. Histological analysis and suction cutometer analysis were performed. P<0.05 was considered significant on statistical analysis. Results: Dermal thickness was noted to be significantly lower in the DFO cohort than the IR control or vehicle cohort at both 4 and 8 weeks post-treatment (B). Collagen ultrastructure was significantly different between the DFO treatment groups, more closely resembling the normal skin groups, compared to the no patch or vehicle patch groups. (C). Collagen density was also significantly lower in the DFO cohort compared the vehicle or IR control groups (D). CD31+ expression was significantly higher in the DFO group compared to all other conditions except the normal skin (E). DFO also had significantly more elasticity than the IR control or vehicle group (F). Conclusion: DFO effectively treats radiation-induced fibrosis in a porcine model, allowing the skin to more closely resemble normal skin than irradiated skin.
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