Development of artificial bone capable of drug loading using octacalcium phosphate

Abstract

Octacalcium phosphate (OCP) is known as a precursor of hydroxyapatite (HA), and is reported to show high bone-regeneration ability. Porous OCP granules are expected to be drug carriers to treat the bone tumor when anticancer drugs are loaded. When OCP granules loaded with drugs are implanted into a bone defect site, it is expected that drugs are released during the transformation of OCP to HA due to the dissolution of OCP and the difference in the adsorption properties. We investigated the transformation behavior of OCP to HA in vitro, and revealed that the nucleation of HA is the rate-determining step in the transformation of OCP to HA. Based on this knowledge, spherical porous granules composed of OCP and HA (OCP/HA granules) were prepared, expecting that the transformation of OCP to HA is accelerated. When human osteosarcoma cells were cultured in the medium in which the methotrexate-loaded OCP/HA granules were immersed, the cell proliferation was significantly inhibited. The granules released the drug continuously. We successfully prepared spherical porous OCP/HA granules and revealed the potential of the granules as drug carriers for the bone tumor treatment.