Abstract：
PEGylated superoxide dismutase (PEG-SOD) is commonly used as a cytoprotective agent in radiotherapy. However, its effectiveness in preventing radiation dermatitis is limited owing to its poor skin permeability. To address this issue, a PEG-SOD-loaded dissolving microneedle (PSMN) patch was developed to effectively prevent radiation dermatitis. Initially, PSMN patches were fabricated using a template mold method with polyvinylpyrrolidone K90 as the matrix material. PSMNs exhibited a conical shape with adequate mechanical strength to penetrate the stratum corneum. More than 90 % of PEG-SOD was released from the PSMN patches within 30 min. Notably, the PSMN patches showed a significantly higher drug skin permeation than the PEG-SOD solutions, with a 500-fold increase. In silico simulations and experiments on skin pharmacokinetics confirmed that PSMN patches enhanced drug permeation and skin absorption, in contrast to PEG-SOD solutions. More importantly, PSMN patches efficiently mitigated ionizing radiation-induced skin damage, accelerated the healing process of radiation-affected skin tissues, and exhibited highly effective radioprotective activity for DNA in the skin tissue. Therefore, PSMN patches are promising topical remedy for the prevention of radiation dermatitis.
摘要：
聚乙二醇化超氧化物歧化酶（PEG-SOD）通常用作放射疗法中的细胞保护剂。然而,由于其皮肤渗透性差，其预防放射性皮炎的有效性有限。为了解决这个问题，开发了一种载有PEG-SOD的溶解微针（PSMN）贴片以有效预防放射性皮炎。最初，使用模板模具方法以聚乙烯吡咯烷酮K90作为基质材料制造PSMN贴片。PSMN表现出圆锥形状，具有足够的机械强度以穿透角质层。超过90%的PEG-SOD在30分钟内从PSMN贴剂中释放。值得注意的是,PSMN贴剂显示出明显高于PEG-SOD溶液的药物皮肤渗透，增加了500倍。在电脑模拟和皮肤药代动力学实验证实，PSMN贴剂增强药物渗透和皮肤吸收，与PEG-SOD溶液相反。更重要的是,PSMN贴片有效缓解电离辐射引起的皮肤损伤，加速受辐射影响的皮肤组织的愈合过程，并对皮肤组织中的DNA表现出高度有效的辐射防护活性。因此,PSMN贴剂是预防放射性皮炎的有希望的局部治疗方法。
