LONG-CIRCULATING NANOPARTICLES BEARING HEPARIN OR DEXTRAN COVALENTLY BOUND TO POLY(METHYL METHACRYLATE)

Purpose. In a biomimetic approach to the development of drug carriers escaping early capture by phagocytes, nanoparticles made of amphiphili c 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. Methods. Owing to the fluorescen t properties of the covalently attached N-vinyl carbazole, the particl es could be detected directly in mouse plasma. Samples were drawn at d ifferent time intervals and fluorescence was recorded. Results. 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 an d were still detectable in the plasma at 72 h. Dextran nanoparticles w ere also eliminated very slowly over 48 h. Bare poly (methyl methacryl ate) nanoparticles were found to have a half-life of only 3 min. Concl usions. Both types of nanoparticles proved to be long-circulating. The potent capacity for opsonisation of the poly(methyl methacrylate) cor e were hidden by the protective effect of either polysaccharide, proba bly due to a dense brush-like structure. In the case of heparin nanopa rticles, the ''stealth'' effect was probably increased by its inhibiti ng properties against complement activation.