title: In vitro study of the specific interaction between poly(2-dimethylamino ethylmethacrylate) based polymers with platelets and red blood cells.
abstract: Poly(2-dimethylamino)ethyl methacrylate (PDMAEMA) is an attractive polycation frequently proposed as a non-viral vector for gene therapy. As expected for other cationic carriers, intravenous administration of PDMAEMA can result in its ionic complexation with various negatively charged domains found within the blood. To gain more insight into this polycation hemoreactivity, we followed the binding kinetics of a free form (FF) of fluorescein labelled PDMAEMA (Mn below 15 kDa) in normal human blood using flow cytometry. This in vitro study highlighted that platelets display higher affinity for this polycation compared to red blood cells (RBCs), with an adsorption isotherm characteristics of a specific saturable binding site. PDMAEMA (1-20 μg/mL) exerted a concentration dependent proaggregant effect with a biphasic aggregation of washed platelets. Activation of platelets was also noticed in whole blood with the expression of P-selectin and fibrinogen on platelet surface. Although additional studies would be needed in order to elucidate the mechanism of PDMAEMA mediated activation of platelets, our manuscript provides important information on the hemoreactivity of FF PDMAEMA.
authors.affiliation: Interfacultary Research Center of Biomaterials, University of Liège, Institute of Chemistry, Building B6C, Sart-Tilman, Liège 4000, Belgium. Electronic address: luca.flebus@ulg.ac.be.
authors.forename: Luca
authors.initials: L
authors.lastname: Flebus
authors.affiliation: Interfacultary Research Center of Biomaterials, University of Liège, Institute of Chemistry, Building B6C, Sart-Tilman, Liège 4000, Belgium. Electronic address: flombart@ulg.ac.be.
authors.forename: François
authors.initials: F
authors.lastname: Lombart
authors.affiliation: Interfacultary Research Center of Biomaterials, University of Liège, Institute of Chemistry, Building B6C, Sart-Tilman, Liège 4000, Belgium. Electronic address: luciaamine.martinezjothar@alumni.ulg.ac.be.
authors.forename: Lucía
authors.initials: L
authors.lastname: Martinez-Jothar
authors.affiliation: Interfacultary Research Center of Biomaterials, University of Liège, Institute of Chemistry, Building B6C, Sart-Tilman, Liège 4000, Belgium. Electronic address: csevrin@ulg.ac.be.
authors.forename: Chantal
authors.initials: C
authors.lastname: Sevrin
authors.affiliation: Laboratory of Thrombosis and Haemostasis, GIGA-Cardiovascular Sciences, University of Liège, Belgium. Electronic address: c.delierneux@doct.ulg.ac.be.
authors.forename: Céline
authors.initials: C
authors.lastname: Delierneux
authors.affiliation: Laboratory of Thrombosis and Haemostasis, GIGA-Cardiovascular Sciences, University of Liège, Belgium. Electronic address: cecile.oury@ulg.ac.be.
authors.forename: Cécile
authors.initials: C
authors.lastname: Oury
authors.affiliation: Interfacultary Research Center of Biomaterials, University of Liège, Institute of Chemistry, Building B6C, Sart-Tilman, Liège 4000, Belgium. Electronic address: C.Grandfils@ulg.ac.be.
authors.forename: Christian
authors.initials: C
authors.lastname: Grandfils
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008689:Methacrylates / Q000494:pharmacology*; D009757:Nylons / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects
chemical_list: D008689:Methacrylates; D009757:Nylons; D019007:P-Selectin; C407037:poly(2-(dimethylamino)ethyl methacrylate); D005340:Fibrinogen
keywords: Blood cells; Hemocompatibility; Poly(2-dimethylamino-ethylmethacrylate); Polycation