Controlled release of clarithromycin from PLGA microspheres enhances bone regeneration in rabbit calvaria defects

Abstract

This study evaluated the sustained release effect of clarithromycin-loaded in PLGA microspheres in a rabbit calvaria defect model. Four bone defects (ø5.0) were created in the calvaria of New Zealand White rabbits (n521, n57/time point). The defects were randomly designated to four groups. Group 1: No augmentation (sham), Group 2: beta-tricalcium phosphate (b-TCP), Group 3: b-TCP with 0.12 mg clarithromycin, and Group 4: b-TCP with 6.12 mg PLGAmicrospheres loaded with 0.12 mg Clarithromycin. After 2, 4, and 12 weeks of healing, bone regeneration was evaluated using micro-computed tomography (mCT) and histology. Clarithromycin release from PLGA microspheres revealed sustained release for around 4 weeks with 50% release during the first week. Histologically, new bone formation was evident at 2 and 4 weeks of healing in all groups and bone formation increased as a function of healing time. At 12 weeks, Group 4 showed significantly higher amount of newly formed bone compared to Group 1. The mCT showed that Group 4 expressed significantly higher bone formation compared to Group 1 at all time points. The in vivo findings showed that b-TCP with clarithromycin-loaded microspheres can enhance bone formation in bone defects.