Auto-associative heparin nanoassemblies: a biomimetic platform against the heparan sulfate-dependent viruses HSV-1, HSV-2, HPV-16 and RSV

Eur J Pharm Biopharm. 2014 Sep;88(1):275-82. doi: 10.1016/j.ejpb.2014.05.007. Epub 2014 May 14.

Abstract

A new, simple and green method was developed for the manufacturing of heparin nanoassemblies active against the heparan sulfate-dependent viruses HSV-1, HSV-2, HPV-16 and RSV. These nanoassemblies were obtained by the auto-association of O-palmitoyl-heparin and α-cyclodextrin in water. The synthesized O-palmitoyl-heparin derivatives mixed with α-cyclodextrin resulted in the formation of crystalline hexagonal nanoassemblies as observed by transmission electron microscopy. The nanoassembly mean hydrodynamic diameters were modulated from 340 to 659 nm depending on the type and the initial concentration of O-palmitoyl-heparin or α-cyclodextrin. The antiviral activity of the nanoassemblies was not affected by the concentration of the components. However, the method of the synthesis of O-palmitoyl-heparin affected the antiviral activity of the formulations. We showed that reduced antiviral activity is correlated with lower sulfation degree and anticoagulant activity.

Keywords: Glycosaminoglycan; HPV; HSV; Heparin; Nanoassemblies; α-Cyclodextrin.

MeSH terms

  • Animals
  • Anticoagulants / chemistry
  • Antiviral Agents / chemistry
  • Biomimetics / methods*
  • Cell Line, Tumor
  • Cell Survival
  • Chlorocebus aethiops
  • Crystallization
  • HEK293 Cells
  • Heparin / chemistry*
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 2, Human / drug effects*
  • Human papillomavirus 16 / drug effects*
  • Humans
  • Hydrodynamics
  • Microscopy, Electron, Transmission
  • Nanoparticles / chemistry*
  • Nanotechnology
  • Respiratory Syncytial Viruses / drug effects*
  • Swine
  • Vero Cells
  • Water / chemistry
  • alpha-Cyclodextrins / chemistry

Substances

  • Anticoagulants
  • Antiviral Agents
  • alpha-Cyclodextrins
  • Water
  • Heparin
  • alpha-cyclodextrin