Targeted Therapy for Glomerulonephritis Using Arterial Delivery of Encapsulated Etanercept

Int J Mol Sci. 2023 Feb 1;24(3):2784. doi: 10.3390/ijms24032784.

Abstract

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.

Keywords: Enbrel; Freund’s complete adjuvant; acute glomerulonephritis; etanercept; intra-arterial injection; nephritis; polyelectrolyte microcapsules; targeted drug delivery.

MeSH terms

  • Animals
  • Capsules
  • Etanercept / therapeutic use
  • Glomerulonephritis* / pathology
  • Kidney / pathology
  • Kidney Glomerulus / pathology
  • Mice

Substances

  • Etanercept
  • Capsules