PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats

The aim of the present work was to assess the merits of PEGylated poly( lac tic-co-glycolic acid) (PEG-PLGA) nanoparticles as protein and peptide drugs (PPD) carriers. PEG-PLGA copolymer, which could be used to prepare the ste alth nanoparticles or long-circulating nanoparticles, was synthesized with methoxypolyethyleneglycol (MePEG) and PLGA. The structure of PEG-PLGA was c onfirmed with H-1 NMR and Fourier transform infrared (FTIR) spectrum, and m olecular weight was determined by gel permeation chromatography (GPC). Bovi ne serum albumin (BSA), chosen as model protein, was encapsulated within th e stealth nanoparticles with the double emulsion method. The particles were characterized in terms of size, zeta potential and in vitro release of the protein. The biological fate of the BSA-loaded nanoparticles following int ravenous administration was determined over 24 h in rats. The experimental results showed that PEG-PLGA could be obtained by ring-opening polymerizati on of lactide and glycolide in the presence of MePEG. H-1 NMR and FTIR spec trum were consistent with the structure of PEG-PLGA copolymer. Molecular we ight determined by GPC was 50800. The stealth nanoparticles loading BSA cou ld be prepared by the double emulsion technique. The entrapment efficiency was 48.6%, particle size about 200 nm and zeta potential -16.1 mV. BSA rele ase from the stealth nanoparticles showed an initial burst release and then sustained release. PEG-PLGA nanoparticles could extend half-life of BSA fr om 13.6 min of loaded in PLGA nanoparticles to 4.5 h and obviously change t he protein biodistribution in rats compared with that of PLGA nanoparticles . Thus. PEG-PLGA nanoparticles could be an effective carrier for PPD delive ry. (C) 2001 Elsevier Science B.V. All rights reserved.