Effect of copolymer composition on the physicochemical characteristics, in vitro stability, and biodistribution of PLGA–mPEG nanoparticles

The physicochemical properties, the colloidal stability in vitro and the biodistribution properties in mice of different PLGA–mPEG nanoparticle compositions were investigated. The nanoparticles were prepared by a precipitation–solvent evaporation technique. The physical characteristics and the colloidal stability of the PLGA–mPEG nanoparticles were significantly influenced by the composition of the PLGA–mPEG copolymer used to prepare the nanoparticles. PLGA–mPEG nanoparticles prepared from copolymers having relatively high mPEG/PLGA ratios were smaller and less stable than those prepared from copolymers having relatively low mPEG/PLGA ratios. All PLGA–mPEG nanoparticle compositions exhibited prolonged residence in blood, compared to the conventional PLGA nanoparticles. The composition of the PLGA–mPEG copolymer affected significantly the blood residence time and the biodistribution of the PLGA–mPEG nanoparticles in liver, spleen and bones. The in vivo behavior of the different PLGA–mPEG nanoparticle compositions did not appear to correlate with their in vitro stability. Optimum mPEG/PLGA ratios appeared to exist leading to long blood circulation times of the PLGA–mPEG nanoparticles. This may be associated with the effects of the mPEG/PLGA ratio on the density of PEG on the surface of the nanoparticles and on the size of the nanoparticles.