SURFACE MODIFICATION OF POLY(LACTIDE-CO-GLYCOLIDE) NANOSPHERES BY BIODEGRADABLE POLY(LACTIDE)-POLY(ETHYLENE GLYCOL) COPOLYMERS

The modification of surface properties of biodegradable poly(lactide-c o-glycolide) (PLGA) and model polystyrene nanospheres by poly(lactide) -poly(ethlene glycol) (PLA:PEG) copolymers has been assessed using a r ange of in vitro characterization methods followed by in vivo studies of the nanospheres biodistribution after intravenous injection into ra ts. Coating polymers with PLA:PEG ratio of 2:5 and 3:4 (PEG chains of 5000 and 2000 Da, respectively) were studied. The results reveal the f ormation of a PLA:PEG coating layer on the particle surface resulting in an increase in the surface hydrophilicity and decrease in the surfa ce charge of the nanospheres. The effects of addition of electrolyte a nd changes in pH on stability of the nanosphere dispersions confirm th at uncoated particles are electrostatically stabilized, while in the p resence of the copolymers, steric repulsions are responsible for the s tability. The PLA:PEG coating also prevented albumin adsorption onto t he colloid surface. The evidence that this effect was observed for the PLA:PEG 3:4 coated nanospheres may indicate that a poly(ethylene glyc ol) chain of 2000 Da can provide an effective repulsive barrier to alb umin adsorption. The in vivo results reveal that coating of PLGA nanos pheres with PLA:PEG copolymers can alter the biodistribution in compar ison to uncoated PLGA nanospheres. Coating of the model polystyrene na nospheres with PLA:PEG copolymers resulted in an initial high circulat ion level, but after 3 hours the organ deposition data showed values s imilar to uncoated polystyrene spheres. The difference in the biologic al behaviour of coated PLGA and polystyrene nanospheres may suggest a different stability of the adsorbed layers on these two systems. A sim ilar biodistribution pattern of PLA:PEG 3:4 to PEG 2:5 coated particle s may indicate that poly(ethylene glycol) chains in the range of 2000 to 5000 can produce a comparable effect on in vivo behaviour.