Science Medical Center, Saratov State University, 83 Astrakhanskaya Str., 410012 Saratov, Russia.
Institute of Medicine, National Research Ogarev Mordovia State University, 68 Bolshevistskaya Str., 430005 Saransk, Russia.
Int J Mol Sci. 2023 Feb 1;24(3):2784. doi: 10.3390/ijms24032784.
Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of polymer capsule accumulation (2.8 ± 0.4 µm) containing labeled etanercept (100 μg per dose) in the kidneys of mice. The comparison of injection into the renal artery and tail vein shows the significant superiority of the intra-arterial administration strategy. The etanercept retention rate of 18% and 8% ID in kidneys was found 1 min and 1 h after injection, respectively. The capsules were predominantly localized in the glomeruli after injection in mice using a model of acute glomerulonephritis. Histological analysis confirmed a significant therapeutic effect only in animals with intra-arterial administration of microcapsules with etanercept. The proposed strategy combines endovascular surgery and the use of polymer microcapsules containing a high molecular weight drug that can be successfully applied to treat a wide range of kidney diseases associated with glomerular pathology.
在医学实践中,为了帮助患有肾小球肾炎的患者克服症状并预防慢性肾衰竭,会给他们开具复杂的免疫抑制疗法。这种方法需要长期系统地使用强效药物,这会导致严重的副作用。本工作表明,含有标记的依那西普(每次剂量 100μg)的聚合物胶囊(2.8±0.4μm)在小鼠肾脏中的积累具有高效性。将药物注射到肾动脉和尾静脉的比较表明,经动脉内给药策略具有明显优势。在注射后 1 分钟和 1 小时,分别发现肾脏中依那西普的保留率为 18%和 8%ID。在使用急性肾小球肾炎模型的小鼠中,注射后胶囊主要定位于肾小球。组织学分析仅证实了经动脉内给予载有依那西普的微胶囊的动物具有显著的治疗效果。所提出的策略结合了血管内手术和使用含有高分子量药物的聚合物微胶囊,该策略可成功应用于治疗与肾小球病理相关的多种肾脏疾病。