Tzror-Azankot Chen, Anaki Adi, Sadan Tamar, Motiei Menachem, Popovtzer Rachela
Faculty of Engineering and the Institute of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat Gan 5290002, Israel.
Materials (Basel). 2022 Nov 4;15(21):7779. doi: 10.3390/ma15217779.
Hyperphosphatemia is a typical complication of end-stage renal disease, characterized by elevated and life-threatening serum phosphate levels. Hemodialysis does not enable sufficient clearance of phosphate, due to slow cell-to-plasma kinetics of phosphate ions; moreover, dietary restrictions and conventional treatment with oral phosphate binders have low success rates, together with adverse effects. Here, we developed a new concept of phosphate-trapping liposomes, to improve and prolong the control over serum phosphate levels. We designed liposomes modified with polyethylene glycol and encapsulated with the phosphate binder ferric citrate (FC liposomes). These liposomes were found to trap phosphate ions in their inner core, and thereby lower free phosphate ion concentrations in solution and in serum. The FC liposomes showed higher phosphate binding ability as phosphate concentrations increased. Moreover, these liposomes showed a time-dependent increase in uptake of phosphate, up to 25 h in serum. Thus, our findings demonstrate effective long-term phosphate trapping by FC liposomes, indicating their potential to reduce serum phosphate toxicity and improve current management of hyperphosphatemia.
高磷血症是终末期肾病的典型并发症，其特征是血清磷酸盐水平升高并危及生命。由于磷酸根离子从细胞到血浆的动力学缓慢，血液透析无法充分清除磷酸盐；此外，饮食限制和口服磷酸盐结合剂的传统治疗成功率低，且伴有不良反应。在此，我们开发了一种新的磷酸盐捕获脂质体概念，以改善和延长对血清磷酸盐水平的控制。我们设计了用聚乙二醇修饰并包裹有磷酸盐结合剂柠檬酸铁的脂质体（FC脂质体）。发现这些脂质体在其内核中捕获磷酸根离子，从而降低溶液和血清中的游离磷酸根离子浓度。随着磷酸盐浓度的增加，FC脂质体表现出更高的磷酸盐结合能力。此外，这些脂质体对磷酸盐的摄取呈现时间依赖性增加，在血清中长达25小时。因此，我们的研究结果表明FC脂质体能够有效长期捕获磷酸盐，表明它们有潜力降低血清磷酸盐毒性并改善目前高磷血症的治疗。
