Nanohydroxyapatite microspheres as delivery system for antibiotics: release kinetics, antimicrobial activity, and interaction with osteoblasts

Severe periodontitis treatment, where massive alveolar bone loss occurs, involves bone defect filling and intensive systemic log-term antibiotics administration. This study aims at developing novel injectable drug delivery systems (nanohydroxyapatite microspheres) with the drug releasing capability for periodontitis treatment and simultaneously initiating the osteointegration process. Materials were characterized by XRD, SEM, inverted stand optical microscope analysis, and mercury porosimetry method. Amoxicillin, amoxicillin + clavulanic acid, and erythromycin were the antibiotics used. Release properties during 28 days from the hydroxyapatite (HA) granules, and two types of nanoHA microspheres were investigated. Biocompatibility was assessed by cytotoxicity assays. HA granules were inadequate, releasing all antibiotic during the first hours. The concentration of antibiotics released in the first days from HA-2 was higher than from HA-1 microspheres, because of the increased porosity and surface area. The release profiles (fast initial release followed by long-term sustained release) of effective doses of antibiotics make these systems good alternatives for antibiotics delivery. Osteoblasts proliferated well on both types of microspheres, being cell growth enhanced in the presence of antibiotics. Erythromycin presented the most beneficial effect. Combining the sustained antibiotic release with the osteoconduction, resorbability, and potential use as injectable bone filling material of porous HA microspheres, these systems provided a forth fold beneficial effect.