Interactions of nanoparticles bearing heparin or dextran covalently bound to poly(methyl methacrylate) with the complement system.
The efficient uptake of injected nanoparticles by cells of the mononuclear phagocyte system (MPS) limits the development of long-circulating colloidal drug carriers. The complement system plays a major role in the opsonization and recognition processes of foreign materials. Since heparin is an inhibitor of complement activation, nanoparticles bearing heparin covalently bound to poly(methyl methacrylate) (PMMA) have been prepared and their interactions with complement evaluated. The particles retained the complement-inhibiting properties of soluble heparin. Nanoparticles bearing covalently bound dextran instead of heparin were weak activators of complement as compared with crosslinked dextran (Sephadex) or bare PMMA nanoparticles. In addition to the specific activity of bound heparin, the protective effect of both polysaccharides is hypothesized to be due to the presence of a dense brush-like layer on the surface of the particles. Such properties are expected to reduce the uptake by MPS in vivo.
Passirani
C
C
Université Paris-Sud XI-URA CNRS 1218, Physico-Chimie, Pharmacotechnie, Biopharmacie, Châtenay-Malabry, France.
Barratt
G
G
Devissaguet
J P
JP
Labarre
D
D
D003167:Complement Activation / Q000187:drug effects; D003165:Complement System Proteins / Q000187:drug effects*; D003911:Dextrans / Q000008:administration & dosage*; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D010316:Particle Size; D010587:Phagocytosis; D019904:Polymethyl Methacrylate / Q000008:administration & dosage*
D003911:Dextrans; D006493:Heparin; D003165:Complement System Proteins; D019904:Polymethyl Methacrylate