LONG CIRCULATING BIODEGRADABLE POLY(PHOSPHAZENE) NANOPARTICLES SURFACE-MODIFIED WITH POLY(PHOSPHAZENE) POLY(ETHYLENE OXIDE) COPOLYMER

The biodistribution of biodegradable poly(organo phosphazene) nanopart icles surface modified by adsorption of a novel poly(organo phosphazen e)-poly(ethylene oxide) copolymer with a 5000 M-w PEO chain (PF-PEO500 0), following intravenous administration in rats and rabbits, is descr ibed. The data are compared to the biodistribution of poly(organo phos phazene) and poly(lactide-co-glycolide) nanoparticles coated with a te trafunctional copolymer of poly(ethylene oxide)-poly(propylene oxide) ethylenediamine, commercially available as Poloxamine 908. This copoly mer has a PEO chain of the same size as the poly(organo phosphazene)-P EO derivative used. The results in the rat model reveal that poly(orga no phosphazene) nanoparticles with a Poloxamine 908 coating were mainl y captured by the liver, although a retardation in clearance from the systemic circulation was seen. In contrast, the poly(organo phosphazen e) nanoparticles coated with PF-PEO5000 showed a prolonged blood circu lating profile, with only a small amount of the nanoparticles sequeste red by the liver. This indicates the importance of the nature of both the anchoring group and the particle surface on the biological perform ances of the system. Study of the biodistribution of the PF-PEO5000-co ated poly(organo phosphazene) nanoparticles in the rabbit model also i ndicated a prolonged systemic circulation lifetime and reduced liver u ptake, whereby a significant amount of the administered nanoparticles was targeted to the bone marrow. (C) 1997 Elsevier Science Limited. Al l rights reserved.