Hierarchically nanostructured mesoporous carbonated hydroxyapatite microspheres for drug delivery systems with high drug-loading capacity

Hierarchically nanostructured mesoporous carbonated hydroxyapatite microspheres have a great potential for bone-implantable drug-delivery applications due to their large specific surface area, high drug-loading capacity (DLC), good biodegradability and bioactivity. However, monodisperse microspheres have rarely been reported due to the crystal orientation of carbonated hydroxyapatite. Herein, two synthesis strategies including an emulsion method and a hydrothermal method have been developed by using calcium carbonate microspheres as sacrificial templates, and the products are denoted EHMs and HHMs, respectively. Excitingly, the highest DLC of the EHMs (1.95 g vancomycin is loaded per gram of carrier) has been achieved among the reported porous hydroxyapatite so far. As compared with the EHMs, the HHMs have the lower DLC due to the smaller specific surface area and greater crystallinity. The in vitro drug release tests carried out by soaking drug-loaded carriers in simulated body fluid (SBF) reveal that the two drug delivery systems show a slow and sustained release of vancomycin and have the similar drug release trends. During the drug release, the EHMs and HHMs are degraded and converted to the bone-like apatite, which indicate that the two drug carriers have good in vitro bioactivity. In vitro cell experiments demonstrate that the two drug carriers have excellent biocompatibility, which can promote the adhesion and spreading of human bone marrow stromal cells (hBMSCs). Therefore, the two drug carriers, especially the EHMs, are promising for bone-implantable drug-delivery applications.