Preparation and characterization of nanoparticles bearing heparin or dextran covalently-linked to poly(methyl methacrylate).

Nanoparticles have been obtained directly in aqueous media, from amphiphilic copolymers synthesized by radical polymerization of methyl methacrylate (MMA) initiated by Ce(IV) ions in the presence of heparin or dextran. The reaction conditions under which the copolymers spontaneously formed nanoparticles depended on the type of polysaccharide and on the concentrations of the reagents. Fluorescent nanoparticles containing N-vinyl carbazole (NVC), covalently linked to PMMA, were also prepared by random copolymerization of MMA and NVC in similar polymerization systems. The non-fluorescent nanoparticle suspensions were stable for several months without using surfactant. The fluorescent particles were larger and less stable then the unlabelled ones. Since all the particles are monodisperse, and in the submicron range, they can be used as models of drug carriers; the covalently-linked fluorescent species allowing them to be followed in vivo. The average molecular weights of the PMMA blocks of the copolymers and of oxidized heparin and dextran were determined by viscometry and/or gel permeation chromatography. The antithrombic activity of oxidized heparin was measured. The results show that the polysaccharide chains were cleaved by Ce(IV) in aqueous nitric acid, resulting in formation of block copolymers made of one or two blocks of PMMA linked to the ends of one polysaccharide block. Taken together, the results suggest that the particles were organized with the polysaccharidic moieties on the surface of the particles and the more hydrophobic PMMA or P(MMA-co-NVC) in the core, in a brush-like structure. This should confer 'stealth' properties to such particles.