The Clinical Implication of Vitamin D Nanomedicine for Peritoneal Dialysis-Related Peritoneal Damage

Int J Nanomedicine. 2019 Dec 5:14:9665-9675. doi: 10.2147/IJN.S215717. eCollection 2019.

Abstract

Purpose: Vitamin D is a novel potential therapeutic agent for peritoneal dialysis (PD)-related peritoneal fibrosis, but it can induce hypercalcemia and vascular calcification, which limits its applicability. In this study, we create nanotechnology-based drug delivery systems to investigate its therapeutics and side effects.

Materials and methods: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino-(polyethylene glycol)2000] (DSPE-PEG) and L-α-phosphatidylcholine (PC), which packages with 1α,25(OH)2D3, were used to construct vitamin D nanoliposomes. To confirm the function and safety of vitamin D nanoliposomes, peritoneal mesothelial cells were treated with TGF-β1 and the reverse was attempted using vitamin D nanoliposomes. Antibodies (Ab) against the peritoneum-glycoprotein M6A (GPM6A) Ab were conjugated with vitamin D nanoliposomes. These particles were implanted into mice by intraperitoneal injection and the animals were monitored for the distribution and side effects induced by vitamin D.

Results: Vitamin D nanoliposomes were taken up by the mesothelial cells over time without cell toxicity and it also provided the same therapeutic effect in vitro. In vivo study, fluorescent imaging showed vitamin D nanoliposomes allow specific peritoneum target effect and also ameliorate vitamin D side effect.

Conclusion: Nanoliposomes vitamin D delivery systems for the prevention of PD-related peritoneal damage may be a potential clinical strategy in the future.

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

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Drug Liberation
  • Epithelial-Mesenchymal Transition / drug effects
  • Humans
  • Kinetics
  • Liposomes
  • Mice
  • Nanomedicine*
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Peritoneal Dialysis / adverse effects*
  • Peritoneum / drug effects
  • Peritoneum / pathology*
  • Phosphatidylethanolamines / chemistry
  • Polyethylene Glycols / chemistry
  • Transforming Growth Factor beta1 / metabolism
  • Vitamin D / pharmacology*

Substances

  • Antibodies
  • Liposomes
  • Phosphatidylethanolamines
  • Transforming Growth Factor beta1
  • polyethylene glycol-distearoylphosphatidylethanolamine
  • Vitamin D
  • Polyethylene Glycols
  • polyethylene glycol 2000