Nano-Calcium Sulfate as a Local Delivery System for Antibiotics

Introduction: Calcium sulfate has long been used as a bone graft substitute and recently a nano-sized product (nCS) with improved properties as an osseous scaffold has been fabricated. The aim of this study was to evaluate the potential of nCS to serve as a delivery system for antibiotics commonly used in osseous related infections. The release kinetics of minocycline (MINO) and doxycycline (DOXY) from preloaded nCS, and the setting time and hardness properties of nCS with the antibiotics were evaluated. The effects of nCS with DOXY and nCS with MINO at various doses were studied with respect to osteoblastic cell activity and differentiation. Methods: For the antibiotic release experiment, discs of nCS mixed with either MINO or DOXY were suspended in phosphate buffered saline and whole aliquots were withdrawn at time intervals (0-10 days). The concentration of the released drug was determined by UV-Visible spectroscopy. Viability of osteoblast cells was tested with a MTT assay and differentiation with a biochemical/colorimetric assay for alkaline phosphatase. Results and Conclusion: DOXY and MINO release from nCS had an initial burst release (∼60%) within the first 24 hrs, followed by sustained release for 7 days. The MTT assay showed that lower doses of nCS-DOXY increased cellular viability compared to controls while higher doses of the antibiotic decreased this response. nCS-MINO did not result in increases in cell viability at any of the doses tested but higher doses resulted in decreased viability. A range of doses of nCS-DOXY resulted in higher ALP activity compared to controls while incubation with nCS-MINO over that same range did not produce any significant effects on this differentiation parameter. nCS has the potential to be used as an antibiotic releasing bone graft material and when preloaded with appropriate concentrations of either DOXY or MINO can support osteoblastic cell activity.