Long-circulating nanoparticles bearing heparin or dextran covalently bound to poly(methyl methacrylate).

In a biomimetic approach to the development of drug carriers escaping early capture by phagocytes, nanoparticles made of amphiphilic copolymers of either heparin or dextran and methyl methacrylate were evaluated relative to their in vivo blood circulation time. They were compared to bare PMMA nanoparticles.Owing to the fluorescent properties of the covalently attached N-vinyl carbazole, the particles could be detected directly in mouse plasma. Samples were drawn at different time intervals and fluorescence was recorded.After an initial phase of elimination from the blood with a half-life of 5 h, the remaining heparin nanoparticles circulated for more than 48 h and were still detectable in the plasma at 72 h. Dextran nanoparticles were also eliminated very slowly over 48 h. Bare poly (methyl methacrylate) nanoparticles were found to have a half-life of only 3 min.Both types of nanoparticles proved to be long-circulating. The potent capacity for opsonisation of the poly(methyl methacrylate) core were hidden by the protective effect of either polysaccharide, probably due to a dense brush-like structure. In the case of heparin nanoparticles, the "stealth" effect was probably increased by its inhibiting properties against complement activation.