Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, China.
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, China.
Int J Pharm. 2022 Sep 25;625:122136. doi: 10.1016/j.ijpharm.2022.122136. Epub 2022 Aug 24.
Although deferoxamine (DFO) has been approved for the treatment the iron overloaded diseases, its clinical application is impeded by very short circulation time and its relating toxicity. In this work, the fluorene methoxycarbonyl (FMOC) for "albumin hitchhiking" was used to prolong the plasma circulation time of DFO and reduce toxicity. The designed FMOC-PEG-DFO conjugates were found to reversible bind to albumin and gradually release DFO in vivo. Herein, the FMOC-PEG-DFO conjugates could increase 30 times the blood circulation time of DFO with the improvement of the iron elimination efficacy. Meanwhile, the conjugates markedly reduced the cytotoxicity of DFO. Taken together, the result demonstrated the FMOC-PEG-DFO conjugates could be a potential therapeutic choice for iron-overload-related diseases.
尽管去铁胺（DFO）已被批准用于治疗铁过载疾病，但由于其循环时间短和相关毒性，其临床应用受到阻碍。在这项工作中，芴甲氧羰基（FMOC）用于“白蛋白搭便车”，以延长 DFO 的血浆循环时间并降低其毒性。所设计的 FMOC-PEG-DFO 缀合物被发现可与白蛋白可逆结合，并在体内逐渐释放 DFO。在此，FMOC-PEG-DFO 缀合物可将 DFO 的血液循环时间延长 30 倍，同时提高铁清除效果。同时，缀合物显著降低了 DFO 的细胞毒性。总之，该结果表明 FMOC-PEG-DFO 缀合物可能是一种治疗与铁过载相关疾病的潜在治疗选择。
