POLYSTYRENE-POLY(ETHYLENE GLYCOL) (PS-PEG2000) PARTICLES AS MODEL SYSTEMS FOR SITE-SPECIFIC DRUG-DELIVERY .2. THE EFFECT OF PEG SURFACE-DENSITY ON THE IN-VITRO CELL-INTERACTION AND IN-VIVO BIODISTRIBUTION

The effect of differing densities of poly (ethylene glycol-2000) (PEG2 000) at the particle surface of polystyrene-poly (ethylene glycol-2000 ) (PS-PEG2000) particles was assessed in terms of hydrophobic interact ion chromatography (HIC) and the in vitro and in vivo behaviour of the particles. The particles, with different surface densities of PEG, we re prepared by varying the copolymerizing reaction of styrene with a P EG macromonomer. There is a clear relationship between the surface den sity of PEG as determined by X-ray photoelectron spectroscopy and surf ace hydrophobicity as assessed by hydrophobic interaction chromatograp hy (HIC). Similarly, the interaction of the particles with non-parench ymal liver cells in in vitro studies was shown to decrease as the surf ace density of PEG increases. The in vivo study investigating the biod istribution of the PS-PEG particles after intravenous injection into r ats reveals that a relationship exists between the surface density of PEG and the extent to which the particles remain in the circulation, a voiding recognition by the reticuloendothelial system. Particles with the higher surface densities show increased circulatory times which co mpared well with data for particles prepared with the surface adsorbed PEO-PPO block copolymer, Poloxamine 908.