Protein encapsulation within poly(ethylene glycol)-coated nanospheres. II.Controlled release properties

The development of injectable nanoparticulate "stealth" carriers for protei n delivery is a major challenge. The aim of this work was to investigate th e possibility of achieving the controlled release of a model protein, human serum albumin (HSA), from poly(ethylene glycol) (PEG)coated biodegradable nanospheres (mean diameter of about 200 nm) prepared from amphiphilic diblo ck PEG-poly(lactic acid) (PLA) copolymers. HSA was efficiently incorporated into the nanospheres, reaching loadings as high as 9% (w/w). Results of th e in vitro release studies showed that it is possible to control the HSA re lease by choosing the appropriate nanosphere size, loading, and composition . These results also revealed that, following their release, HSA molecules readsorbed onto the nanospheres surfaces when they were not protected by a PEG coating. We were surprised to observe that in spite of the water uptake of the PLA-PEG nanospheres [11-29% (w/w)], the copolymer did not significa ntly degrade after a 15-day incubation period. Therefore, we concluded that during this time HSA release from PLA-PEG nanospheres followed a diffusion mechanism where bulk erosion and surface desorption were negligible. (C) 1 999 John Wiley & Sons, Inc.