- A sustained delivery system for interleukin-1 receptor antagonist (IL-1Ra) may have great therapeutic and industrial potential due to the cytokine activity as an IL-1 inhibitor. Here, we investigated the capability of biodegradable polymeric microspheres to sustain the release and prolong the therapeutic efficacy of IL-1Ra. IL-1Ra was encapsulated within rapidly degrading poly(lactic/glycolic acid) PLGA RG502H microspheres, which showed a desirable release profile of IL-1Ra in vitro. Pharmacokinetic study in mice revealed elevated serum levels of the recombinant IL-1Ra (rIL-1Ra) for up to 8 days following subcutaneous injection of IL-1Ra microspheres. In comparison, the serum levels of rIL-1Ra following subcutaneous or intravenous bolus injection of the soluble cytokine decreased very rapidly; within 48 h no recombinant cytokine was detected in mice sera. The sustained delivery of rIL-1Ra for over two weeks was efficient in inhibiting IL-1ß-stimulated induction of serum IL-6. These results suggest that the present therapeutic protocol of daily bolus injections of the IL-1Ra may be replaced by a weekly injection of IL-1Ra within PLGA RG502H microspheres.