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

Nanoparticles have been obtained directly in aqueous media, from amphiphili c copolymers synthesized by radical polymerization of methyl methacrylate ( MMA) initiated by Ce(IV) ions in the presence of heparin or dextran. The re action conditions under which the copolymers spontaneously formed nanoparti cles depended on the type of polysaccharide and on the concentrations of th e reagents. Fluorescent nanoparticles containing N-vinyl carbazole (NVC), c ovalently linked to PMMA, were also prepared by random copolymerization of MMA and NVC in similar polymerization systems. The non-fluorescent nanopart icle suspensions were stable for several months without using surfactant. T he fluorescent particles were larger and less stable then the unlabelled on es. Since all the particles are monodisperse, and in the submicron range, t hey can be used as models of drug carriers; the covalently-linked fluoresce nt species allowing them to be followed in vivo. The average molecular weig hts of the PMMA blocks of the copolymers and of oxidized heparin and dextra n were determined by viscometry and/or gel permeation chromatography. The a ntithrombic activity of oxidized heparin was measured. The results show tha t 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 PMM A linked to the ends of one polysaccharide block. Taken together, the resul ts suggest that the particles were organized with the polysaccharidic moiet ies 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.