GRGDS-functionalized chitosan nanoparticles as a potential intravenous hemostat for traumatic hemorrhage control in an animal model

Nanomedicine. 2018 Nov;14(8):2531-2540. doi: 10.1016/j.nano.2018.08.007. Epub 2018 Sep 5.

Abstract

Hemostats, which are used for immediate intervention during internal hemorrhage in order to reduce resulting mortality and morbidity, are relatively rare. Here, we describe novel intravenous nanoparticles (CPG-NPs-2000) with chitosan succinate (CSS) as cores, polyethylene glycol (PEG-2000) as spacers and a glycine-arginine-glycine-aspartic acid-serine (GRGDS) peptide as targeted, active hemostatic motifs. CPG-NPs-2000 displayed significant hemostatic efficacy, compared to the saline control, CSS nanoparticles, and tranexamic acid in liver trauma rat models. Further studies have demonstrated that CPG-NPs-2000 are effectively cleared from organs and blood, within 2 and 48 h, respectively. In addition, administration of CPG-NPs-2000 does not affect clotting function under normal physiological conditions, indicating their potential safety in vivo. CPG-NPs-2000 exhibit excellent thermal stability, good solubility, and redistribution ability, in addition to being low cost. These characteristics indicate that CPG-NPs-2000 may have strong potential as effective intravenous hemostats for treating severe internal bleeding.

Keywords: Chitosan; Hemorrhage; Intravenous hemostat; Nanoparticle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chitosan / chemistry*
  • Disease Models, Animal*
  • Female
  • Hemorrhage / pathology
  • Hemorrhage / therapy*
  • Hemostatics / therapeutic use*
  • Liver / drug effects
  • Liver / injuries*
  • Male
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Oligopeptides / chemistry*
  • Polyethylene Glycols / chemistry
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Hemostatics
  • Oligopeptides
  • Polyethylene Glycols
  • Chitosan
  • glycyl-arginyl-glycyl-aspartyl-serine