Targeted anti-inflammatory peptide delivery in injured endothelial cells using dermatan sulfate/chitosan nanomaterials

Carbohydr Polym. 2020 Feb 15:230:115610. doi: 10.1016/j.carbpol.2019.115610. Epub 2019 Nov 14.

Abstract

This work describes a novel delivery system for targeting egg-derived anti-inflammatory tripeptide Ile-Arg-Trp (IRW) to endothelial cells. The nanomedicine is synthesized by a simple and reproducible ionotropic gelification method that results in the efficient loading of the positively charged IRW within the dermatan sulfate/ chitosan matrix, as demonstrated by ss-NMR spectroscopy. The incorporation of IRW results in a stable nanoparticle dispersion with a single size population of 442 ± 43 nm. Fluorescence microscopy studies demonstrate the capacity of the nanomaterial to distinguish between a quiescent and an injured endothelium through the interaction of dermatan sulfate with the CD44 receptor. Remarkably, no additional surface functionalization is required as dermatan sulfate mediates their internalization and the intracellular release of this natural anti-inflammatory tripeptide to modulate endothelial inflammatory response. This simple, scalable, and versatile nanotechnology platform opens new opportunities to apply in the therapy of vascular disease.

Keywords: Anti-inflammatory peptide; Chitosan; Dermatan sulfate; Endothelial cells; Polyelectrolyte complex.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Cells, Cultured
  • Chitosan / analogs & derivatives*
  • Dermatan Sulfate / chemistry*
  • Drug Liberation
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hyaluronan Receptors / metabolism
  • Mice
  • Nanoparticles / chemistry*
  • Oligopeptides / administration & dosage*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Protein Binding

Substances

  • Anti-Inflammatory Agents
  • Hyaluronan Receptors
  • Oligopeptides
  • Dermatan Sulfate
  • Chitosan