Auto-associative heparin nanoassemblies: a biomimetic platform against the heparan sulfate-dependent viruses HSV-1, HSV-2, HPV-16 and RSV.
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.
University of Turin, Department of Clinical and Biological Sciences, Torino, Italy.
David
D
Lembo
University of Turin, Department of Clinical and Biological Sciences, Torino, Italy.
Manuela
M
Donalisio
Univ Paris-Sud, Institut Galien Paris Sud, UMR CNRS 8612, Faculté de Pharmacie, Châtenay-Malabry cedex, France.
Claire
C
Laine
University of Turin, Department of Clinical and Biological Sciences, Torino, Italy.
Valeria
V
Cagno
University of Turin, Department of Clinical and Biological Sciences, Torino, Italy.
Andrea
A
Civra
Univ Paris Sud, Laboratoire d'hématologie, Faculté de Pharmacie, Châtenay-Malabry cedex, France.
Elsa P
EP
Bianchini
Univ Paris-Sud, Institut Galien Paris Sud, UMR CNRS 8612, Faculté de Pharmacie, Châtenay-Malabry cedex, France.
Narimane
N
Zeghbib
Univ Paris-Sud, Institut Galien Paris Sud, UMR CNRS 8612, Faculté de Pharmacie, Châtenay-Malabry cedex, France. Electronic address: kawthar.bouchemal@u-psud.fr.
Kawthar
K
Bouchemal
D000818:Animals; D000925:Anticoagulants / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry; D032701:Biomimetics / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002522:Chlorocebus aethiops; D003460:Crystallization; D057809:HEK293 Cells; D006493:Heparin / Q000737:chemistry*; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D052162:Human papillomavirus 16 / Q000187:drug effects*; D006801:Humans; D057446:Hydrodynamics; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D013552:Swine; D014709:Vero Cells; D014867:Water / Q000737:chemistry; D047391:alpha-Cyclodextrins / Q000737:chemistry
D000925:Anticoagulants; D000998:Antiviral Agents; D047391:alpha-Cyclodextrins; D014867:Water; D006493:Heparin; C032613:alpha-cyclodextrin
Glycosaminoglycan; HPV; HSV; Heparin; Nanoassemblies; α-Cyclodextrin