Cationic derivatives of dextran and hydroxypropylcellulose as novel potential heparin antagonists

J Med Chem. 2011 Oct 13;54(19):6586-96. doi: 10.1021/jm200380w. Epub 2011 Sep 6.

Abstract

Cationic derivatives of dextran (Dex) and hydroxypropylcellulose (HPC) were studied as potential alternatives of protamine sulfate (PS) used in the reversal of anticoagulant activity of heparin. The modification was performed by the attachment of cationic groups to the Dex main chain or by grafting short side chains of a polycation onto HPC. The cationic derivatives of these polysaccharides were found to bind heparin with the efficiency increasing with growing degree of cationic modification. The degree of cationic modification and consequently the ζ potential of the polymers do not have to be high to achieve effective heparin binding. The size of the complexes of cationic Dex with unfractionated heparin (UFH) is a few micrometers. For complexes of cationic HPC and UFH the size is much below 1 μm, both below and above the lower critical solution temperature of HPC. None of the cationic polysaccharides studied caused hemolysis. The concentrations of the polymers inducing the aggregation of human erythrocytes in vitro were determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations
  • Cellulose / analogs & derivatives*
  • Cellulose / chemical synthesis
  • Cellulose / chemistry
  • Cellulose / pharmacology
  • Dextrans / chemical synthesis*
  • Dextrans / chemistry
  • Dextrans / pharmacology
  • Erythrocyte Aggregation / drug effects
  • Hemolysis
  • Heparin / chemistry
  • Heparin Antagonists / chemical synthesis*
  • Heparin Antagonists / chemistry
  • Heparin Antagonists / pharmacology
  • Humans
  • In Vitro Techniques
  • Light
  • Quaternary Ammonium Compounds / chemical synthesis*
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / pharmacology
  • Scattering, Radiation
  • Structure-Activity Relationship

Substances

  • Cations
  • Dextrans
  • Heparin Antagonists
  • Quaternary Ammonium Compounds
  • Cellulose
  • Heparin
  • hydroxypropylcellulose