SURFACE MODIFICATION OF NANOPARTICLES BY PEO PPO BLOCK-COPOLYMERS TO MINIMIZE INTERACTIONS WITH BLOOD COMPONENTS AND PROLONG BLOOD-CIRCULATION IN RATS

The biological fate of injected foreign particles is believed to be cl osely related to their interactions with blood plasma proteins and cel ls. In order to verify this correlation, we have quantitatively measur ed protein adsorption and blood retention profiles in rats by using mo del polystyrene latex nanoparticles. The in vitro interactions of thes e non-biodegradable particles with plasma proteins and whole blood can be altered by modifying their surfaces with a family of amphiphilic p olymeric surfactants, PEO/PPO Pluronic or Tetronic block copolymers. P rotein adsorption was measured by several techniques, including photon correlation spectroscopy, centrifugation, high performance liquid chr omatography and field-flow fractionation. Pluronic F108 and Tetronic 9 08 and 1508 copolymers (with PEO terminal block MW(PEO) > 5000, PPO mi ddle block MW(PPO) > 3000, and HLB values >24) were shown to be the mo st effective surface modifiers in reducing adsorption of plasma protei ns on the particles. Minimum interaction of coated particles with whol e blood was also observed by optical microscopy. The blood circulation half-life of the particles injected in rats was increased from 20 min to 13 h when the latex particles (75 nm) were precoated with these bl ock copolymers. These results suggest that nanoparticles designed for use as injectable drugs or drug carriers should display similar surfac e characteristics provided by such amphiphilic surface modifiers.