PROTEIN ENCAPSULATION WITHIN POLYETHYLENE GLYCOL-COATED NANOSPHERES -I - PHYSICOCHEMICAL CHARACTERIZATION

The development of injectable nanoparticulate ''stealth'' carriers for protein delivery is a major challenge. We have shown the possibility of entrapping human serum albumin (HSA) in polyethylene glycol (PEG)-c oated mono-disperse biodegradable nanospheres with a mean diameter of about 200 nm, prepared from amphiphilic diblock PEG-polylactic acid (P LA) copolymers, with loadings up to 9% (w/w). Microscopic techniques a nd surface analysis studies enabled us to prove that the protein was w ell entrapped and not adsorbed onto the particle surface. Zeta potenti al and water uptake studies corroborated that part of the PEG chains a re located in the nanosphere matrix. Water uptake in the nanospheres w as related to their chemical composition, i.e., the respective wt% of PEG and PLA in the matrix, and not on their fabrication procedure. Phe hydrophilic PEG blocks absorbed up to 130% (w/w) water, whereas PLA a bsorbed only about 10% (w/w). However, the rate of swelling at the beg inning of the process was related to the structure of the matrix, more particularly to the manner in which PEG was disposed at the surface. Furthermore, it was shown that the PEG ''brush'' at the nanosphere sur face drastically reduces HSA adsorption on the PEG-PLA nanospheres com pared to the PLA ones. (C) 1998 John Wiley & Sons, Inc.