Sequential release of double drug (graded distribution) loaded gelatin microspheres/PMMA bone cement

Drugs are loaded into PMMA bone cement to reduce the risk of infection in freshly implanted prostheses or to promote the differentiation and growth of osteoblasts. However, the same method of loading of drugs in the bone cement cannot simultaneously achieve an effective antibacterial response and long-term treatment outcomes for osteoporosis based on a patient's clinical needs. In the present study, gentamicin sulfate (GS)/alendronate (ALN)-dual-loaded gelatin modified PMMA bone cement (GAPBC) was fabricated to provide rapid and continuous antibiotic release and long-term anti-osteoporotic therapy. Specifically, the gelatin microspheres were loaded with the drugs using separate methodologies, namely, ALN was loaded during fabrication of the gelatin microspheres after which GS was absorbed onto the gelatin from solution. The results demonstrate that sequential release of the GS and ALN was achieved, GS release playing a major role over the first 24 hours and ALN release dominant after 3 weeks of immersion in PBS, resulting from the graded distribution within the gelatin microspheres, and the final drug release ratio of GS (73.6%) and ALN (68.5%) from the modified bone cement was significantly higher than from PMMA bone cement. Therefore, GAPBC represents a potential drug carrier for future clinical applications.