Fabrication and characterization of hydroxyapatite/sodium alginate/chitosan composite microspheres for drug delivery and bone tissue engineering.

Hydroxyapatite/sodium alginate/chitosan (HA/SA/CS) composite microspheres, which possess good biocompatibility for specific biomedical application, were prepared using an emulsion crosslink technique; calcium ions were used as a cross-linking agent. The effect of the concentration of sodium alginate (SA), the volume ratio of water to oil, the content of hydroxyapatite (HA) nanoparticles, as well as rotation speed, on the morphology and dispersion of composite microspheres were investigated. Also investigated were the drug loading, release behaviors, in vitro hemolysis activity, cytotoxicity, cell adhesion and proliferation capacity of the materials. The results demonstrate that the HA/SA/CS composite microspheres were successfully prepared; their drug loading and encapsulation efficiency are much higher than that of HA nanoparticles. Dox-loaded HA/SA/CS composite microspheres show good pH-sensitive drug-release capability. The hemolysis and cytotoxicity tests suggest that the microspheres have good blood and cell compatibility. Furthermore, the prepared composite microspheres display better cell adhesion and proliferation capacity than HA nanoparticles and HA/SA composite microspheres. Therefore, the HA/SA/CS composite microspheres might have potential as drug carriers in a pH-responsive controlled-release drug delivery system and as candidates for application in bone tissue engineering.