Multi-loaded ceramic beads/matrix scaffolds obtained by combining ionotropic and freeze gelation for sustained and tuneable vancomycin release

Abstract

For a targeted release against bacteria-associated bone diseases (osteomyelitis) ceramic beads with a high drug loading capacity, loaded with vancomycin as model antibiotic, are synthesized as drug carrier and successfully incorporated in an open porous hydroxyapatite matrix scaffold via freeze gelation to prevent bead migration at the implantation site and to extend drug release. We demonstrate that the quantity of loaded drug by the hydroxyapatite and β-tricalcium phosphate beads, produced by ionotropic gelation, as well as drug release can be tuned and controlled by the selected calcium phosphate powder, sintering temperature, and high initial vancomycin concentrations (100mg/ml) used for loading. Bead pore volume up to 68mm3/g, with sufficiently large open pores (pore size of up to 650nm with open porosity of 72%) and high surface area (91m2/g) account likewise for a maximum drug loading of 236mg/g beads or 26mg/sample. Multi-drug loading of the beads/matrix composite can further increase the maximum loadable amount of vancomycin to 37mg/sample and prolong release and antibacterial activity on Bacillus subtilis up to 5days. The results confirmed that our approach to incorporate ceramic beads as drug carrier for highly increased drug load in freeze-gelated matrix scaffolds is feasible and may lead to a sustained drug release and antibacterial activity.