Microspheres of alginate encapsulated minocycline-loaded nanocrystalline carbonated hydroxyapatite: therapeutic potential and effects on bone regeneration

Mônica Diuana Calasans-Maia,1 Carlos Alberto Brazil Barboza Junior,2 Carlos Alberto Soriano-Souza,3 Adriana Terezinha Neves Novellino Alves,4 Marcelo Jose de Pinheiro Uzeda,1 Victor R Martinez-Zelaya,3 Elena Mavropoulos,3 Maria Helena Rocha Leão,5 Ronaldo Barcellos de Santana,2 Jose Mauro Granjeiro,1 Alexandre Malta Rossi31Clinical Research in Dentistry Laboratory, School of Dentistry, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil; 2Department of Periodontology, School of Dentistry, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil; 3Department of Condensed Matter, Applied Physics and Nanoscience, Brazilian Center for Research in Physics, Rio de Janeiro, Brazil; 4Department of Stomatology. School of Dentistry, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil; 5Department of Biochemical Engineering, School of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilBackground and objective: Tetracycline and its derivatives, combined with calcium phosphates, have been proposed as a delivery system to control inflammatory processes and chronic infections. The objective of this study was to evaluate the microspheres of alginate encapsulated minocycline-loaded nanocrystalline carbonated hydroxyapatite (CHAMINO) as a biomimetic device to carry out target-controlled drug delivery for alveolar bone repair.Methods: CHAMINO microspheres were implanted in a rat central incisor socket after 7 and 42 days. New bone was formed in both groups between 7 and 42 days of implantation. However, the bone growth was significantly higher for the CHAMINO microspheres.Results: The minocycline (MINO) loading capacity of the nanocrystaline carbonated hydroxyapatite (CHA) nanoparticles was 25.1±2.2 μg MINO/mg CHA for adsorption over 24 hrs. The alginate microspheres containing minocycline-loaded CHA were biologically active and inhibited the Enterococcus faecalis culture growth for up to seven days of the MINO release. An osteoblastic cell viability assay based on the resazurin reduction was conducted after the cells were exposed to the CHAMINO powder and CHAMINO microspheres. Thus, it was found that the alginate extracts encapsulated the minocycline-loaded CHA microspheres and did not affect the osteoblastic cell viability, while the minocycline-doped CHA powder reduced the cell viability by 90%.Conclusion: This study concluded that the alginate microspheres encapsulating the minocycline-loaded nanocrystalline carbonated hydroxyapatite exhibited combined antibacterial activity against Enterococcus faecalis with cytocompatibility and osteoconduction properties. The significant improvement in the new bone formation after 42 days of implantation suggests that the CHAMINO microsphere has potential in clinical applications of bone regeneration.Keywords: nanomaterials, carbonated hydroxyapatite, minocycline, biocompatibility, bone regeneration