Injectable microsphere/hydrogel combination systems for localized protein delivery

Injectable delivery systems for therapeutic proteins (e.g., hydrogels and microspheres) have attracted wide attention. Hydrogels, however, may release their hydrophilic contents too rapidly in a large initial burst, and phagocytes may clear microspheres within a relatively short time period after administration. We hypothesized that microsphere/hydrogel combination systems could achieve a controlled and sustained release of proteins as an injectable delivery system. To test this hypothesis, we prepared PLGA microspheres containing a model protein and mixed these with alginate gels. The mixing ratio of the components was the primary controlling parameter of the protein release. This approach could be useful for development of injectable and localized drug delivery systems.