Protein instability during microencapsulation has been one of the major drawbacks of protein delivery systems. In this study, the effects of various excipients (poly vinyl alcohol, glucose, starch, heparin) on the stability of encapsulated human immunoglobulin G (IgG) in poly(epsilon-caprolactone) (PCL) microspheres and on microsphere characteristics were investigated before and after gamma-sterilization. Microspheres formulated without any excipients and with glucose had a mean particle size around 3-4 mu m whereas the mean particle sizes of other microspheres were around 5-6 mu m. Use of PVA significantly increased the IgG-loading and encapsulation efficiency of microspheres. After gamma-irradiation, IgG stability was mostly maintained in the microspheres with excipients compared to microspheres without any excipients. According to the mu BCA results, microspheres without any excipient showed a high initial burst release as well as a fast release profile among all groups. Presence of PVA decreased the loss in the activity of IgG released before (completely retained after 6 h and 15.69% loss after 7 days) and after gamma-irradiation (26.04% loss and 52.39% loss after 6 h and 7 days, respectively). The stabilization effect of PVA on the retention of the activity of released IgG was found more efficient compared to other groups formulated with carbohydrates. (C) 2014 Elsevier B.V. All rights reserved.