Novel drug delivery system was prepared and evaluated as for application in cancerous bone treatment. It had three stacked layers, including a drug-free layer, a cisplatin-loaded layer, and a curcumin-containing layer. Our previously characterized biomaterials, namely Zr-hydroxyapatite (Zr-HA) and alkaline-treated polycaprolactone (modified-PCL), were used as major components of the drug carrier. Polar-polar interactions between cisplatin and Zr-HA were modulated by the modified-PCL included, leading to increase of cisplatin release. Using β-cyclodextrin (β-CD) to entrap curcumin caused improvement of curcumin solubility and release. The 3D-construct was porous with internal interconnected pores according to SEM micrographs. Large amount of apatite was formed and proteins adsorbed on the scaffolds after immersed in physiologic buffer solution and in medium containing fetal bovine serum, respectively. Optimal concentrations of ascorbic acid and triamcinolone were used for induction of bone marrow stromal cells to become osteoblasts by expressing an enzyme marker, e.g., alkaline phosphatase. The prepared scaffolds were considered osteo-conductive and osteo-inductive. The concentrations of cisplatin and curcumin reached the IC50 of SK-ES-1 cells of osteosarcoma and MCF-7 cells of breast adenocarcinoma after 24 h and 3 days of release, respectively. These cancer cells were more sensitive to the combined cisplatin and curcumin than each of the drugs. Regeneration of new bone and execution of residential cancer cells in defected bone were proposed after replacing the lost bone by this established drug carrier. The assumption needs to be verified in the future using animal models.
Keywords: Drug delivery system; Zr-hydroxyapatite; beta-cyclodextrin; bone regeneration; bone scaffold; cancerous bone; cisplatin; curcumin; polycaprolactone.