Silver nanoparticles (AgNps) were prepared by modified chemical reduction with poly (alpha, gamma, L-glutamic acid) (PGA) as capping agent. These Ag/PGA nanoparticles (AgNpPGAs) were highly stable over long periods of time without signs of precipitation. In addition to obtaining stable AgNpPGAs, a further aim was to examine their encapsulation in the poly(L-lactide-co-glycolide) (PLGA) polymer matrix. The current interest of polymer-AgNps in biomedical applications is because a versatile system must have antimicrobial activity upon target contact, without the release of toxic biocides. The synthesis of these PLGA/AgNpPGAs used physicochemical methods with solvent/non-solvent systems. Degradation of these PLGA/AgNpPGAs and the release rate of their AgNPs were studied in physiological solution over three months. The antimicrobial activity of the samples was investigated towards six laboratory control strains from the American Type Culture Collection (ATCC) and one clinical isolate methicillin-resistant Staphylococcus aureus strain by the broth microdilution method and the results showed superior and extended activity of PLGA/AgNpPGAs. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated good biocompatibility of these PLGA/AgNpPGAs. The formation of intracellular reactive oxygen species was measured spectrophotometrically using a fluorescent probe, which showed that these PLGA/AgNpPGAs are not inducers of such species. The samples were characterized by UV-VIS spectrometry, X-ray diffraction, zeta potential measurements, field-emission scanning electron microscopy, and transmission electron microscopy. (C) 2012 Elsevier Ltd. All rights reserved.