Novel Application of Magnetite Nanoparticle-Mediated Vitamin D3 Delivery for Peritoneal Dialysis-Related Peritoneal Damage

Int J Nanomedicine. 2021 Mar 11:16:2137-2146. doi: 10.2147/IJN.S291001. eCollection 2021.

Abstract

Purpose: Vitamin D3 is useful for the treatment of peritoneal dialysis (PD)-related peritoneal damage, but its side effects, such as hypercalcemia and vascular calcification, limit its applicability. Thus, we developed vitamin D-loaded magnetic nanoparticles (MNPs) and determined their therapeutic efficacy and side effects in vivo.

Materials and methods: Alginate-modified MNPs were combined with 1α, 25 (OH)2D3 to generate vitamin D-loaded nanoparticles. The particles were conjugated with an antibody against peritoneum-glycoprotein M6A (GPM6A). The particles' ability to target the peritoneum was examined following intraperitoneal administration to mice and by monitoring their bio-distribution. We also established a PD animal model to determine the therapeutic and side effects of vitamin D-loaded MNPs in vivo.

Results: Vitamin D-loaded MNPs targeted the peritoneum better than vitamin D3, and had the same therapeutic effect as vitamin D3 in ameliorating peritoneal fibrosis and functional deterioration in a PD animal model. Most importantly, the particles reduced the side effects of vitamin D3, such as hypercalcemia and body weight loss, in mice.

Conclusion: Vitamin D-loaded MNPs could be an ideal future therapeutic option to treat PD-related peritoneal damage.

Keywords: fibrosis; nanoparticles; peritoneal dialysis; vitamin D.

MeSH terms

  • Alginates / chemistry
  • Animals
  • Antibodies / metabolism
  • Cholecalciferol / administration & dosage*
  • Disease Models, Animal
  • Drug Delivery Systems*
  • Drug Liberation
  • Humans
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / ultrastructure
  • Male
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Peritoneal Dialysis / adverse effects*
  • Peritoneal Fibrosis / etiology
  • Peritoneal Fibrosis / pathology
  • Peritoneum / pathology*

Substances

  • Alginates
  • Antibodies
  • Magnetite Nanoparticles
  • Membrane Glycoproteins
  • Cholecalciferol