In recent years, there has been an increase in nanoparticle research towards creating better release systems that can maintains the effective dosage over desired periods. Conventional nanoparticle systems have not been successful for this goal. Thus, the aim of this study is to evaluate the sequential release profiles of hybrid materials, combining nanoparticles, hydrogels and bone cement, for the treatment of arthroplasty infections. In this study, Vancomycin, which is one of the most used antibiotics in orthopedics, was loaded to alginate-chitosan nanoparticles. These drug-loaded nanoparticles were dispersed in an alginate gel and the gel covered the polymethylmethacrylate bone cement. After the crosslinking of the gel around the bone cement, the sequential release profile was evaluated for 60 days in vitro. The results of the morphological, chemical characterization and encapsulations studies showed that different loadings of drugs resulted in different encapsulation efficiencies. Although the release profile from the nanoparticles was as expected, the sequential release profile of the combined system has a Fickian type release for a longer time period. In conclusion, the results indicate that combining different release systems can alter the release profile of the system.