Development of porous apatite ceramic for local delivery of chemotherapeutic agents.
An experimental study was conducted on a drug delivery system (DDS), using porous apatite ceramics (PAC): hydroxyapatite block (HAb) [Ca10(PO4)6(OH)2] having a porosity of 35-48% and pore size range of 50-300 microm, and beta-tricalcium phosphate block (TCP) [Ca3(PO4)2] having a porosity of 75-80% and pore size range of 100-400 microm, for sustained release of a chemotherapeutic agent. Methotrexate (MTX) was loaded in the pores of PAC blocks by centrifuging the blocks in MTX solution. Impregnation of MTX in PAC blocks (1 cm3) was confirmed by a magnetic resonance imaging (MRI) study using Gadolinium-DTPA enhancement. The MRI showed high signal intensity in the PAC, which was confirmed by dye loading into the pores. To estimate the MTX-releasing capability of the PAC, the blocks were stored in 3 mL of phosphate-buffered saline (PBS) at 37 degrees C and the PBS was replaced every 48 h. The amount of MTX released was assayed by high-performance liquid chromatography. This study showed that MTX-impregnated PAC (0.63-2.25 mg/block) released the drug in a steady manner and maintained its concentration (0.1-1.0 microg/mL) up to 12 days. This concentration is high enough to be effective against tumor cells. Chemotherapeutic agent-impregnated PAC, prepared by simple centrifugation, could be a valuable form of local chemotherapy when used as a strut graft to repair bone defects. This new DDS material could also be used as an adjuvant to extended curettage and provide a means to reduce the recurrence of tumors without risk of systemic toxicity.
Itokazu
M
M
Department of Orthopaedic Surgery, Gifu University School of Medicine, Japan.
Sugiyama
T
T
Ohno
T
T
Wada
E
E
Katagiri
Y
Y
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000032:analysis / Q000627:therapeutic use; D001031:Apatites; D001859:Bone Neoplasms / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D008727:Methotrexate / Q000008:administration & dosage* / Q000032:analysis / Q000627:therapeutic use; D012983:Soft Tissue Neoplasms / Q000188:drug therapy
D000964:Antimetabolites, Antineoplastic; D001031:Apatites; D008727:Methotrexate