PDF(Pubmed)
Abstract：
Topical patch delivery of deferoxamine (DFO) has been studied as a treatment for this fibrotic transformation in irradiated tissue. Efficacy of a novel cream formulation of DFO was studied as a RIF therapeutic in unwounded and excisionally wounded irradiated skin. C57BL/6J mice underwent 30 Gy of radiation to the dorsum followed by 4 weeks of recovery. In a first experiment, mice were separated into six conditions: DFO 50 mg cream (D50), DFO 100 mg cream (D100), soluble DFO injections (DI), DFO 1 mg patch (DP), control cream (Vehicle), and irradiated untreated skin (IR). In a second experiment, excisional wounds were created on the irradiated dorsum of mice and then divided into four treatment groups: DFO 100 mg Cream (W-D100), DFO 1 mg patch (W-DP), control cream (W-Vehicle), and irradiated untreated wounds (W-IR). Laser Doppler perfusion scans, biomechanical testing, and histological analysis were performed. In irradiated skin, D100 improved perfusion compared to D50 or DP. Both D100 and DP enhanced dermal characteristics, including thickness, collagen density and 8-isoprostane staining compared to untreated irradiated skin. D100 outperformed DP in CD31 staining, indicating higher vascular density. Extracellular matrix features of D100 and DP resembled normal skin more closely than DI or control. In radiated excisional wounds, D100 facilitated faster wound healing and increased perfusion compared to DP. The 100 mg DFO cream formulation rescued RIF of unwounded irradiated skin and improved excisional wound healing in murine skin relative to patch delivery of DFO.
摘要：
已经研究了去铁胺（DFO）的局部贴剂递送作为在辐照组织中这种纤维化转化的治疗方法。研究了DFO的新型乳膏制剂在未受伤和切除受伤的辐照皮肤中作为RIF治疗剂的功效。C57BL/6J小鼠对背部进行30Gy辐射,随后恢复4周。在第一个实验中，将小鼠分为六个条件：DFO50mg乳膏（D50），DFO100毫克奶油（D100），可溶性DFO进样(DI)，DFO1mg贴片（DP），对照霜（车辆），和照射的未经处理的皮肤(IR)。在第二个实验中,在小鼠的照射后的背部上创建切除伤口，然后分为四个治疗组：DFO100mg乳膏（W-D100），DFO1mg贴片（W-DP），对照霜(W-Vehicle),和照射的未处理伤口(W-IR)。激光多普勒灌注扫描,生物力学测试，并进行组织学分析。在照射过的皮肤中，与D50或DP相比,D100改善了灌注。D100和DP都增强了皮肤特性，包括厚度,与未经处理的辐照皮肤相比，胶原蛋白密度和8-异前列腺素染色。D100在CD31染色中优于DP，表明血管密度较高。D100和DP的细胞外基质特征比DI或对照更接近于正常皮肤。在放射切除伤口中，与DP相比,D100促进更快的伤口愈合和增加的灌注。相对于DFO的贴剂递送,100mgDFO乳膏制剂挽救了未受伤的照射皮肤的RIF,并改善了鼠皮肤中的切除伤口愈合。
