ABSTRACT
We performed an experimental study on a new drug delivery system that employs a porous hydroxyapatite block (HAb) (composition: Ca10(PO4)6(OH)2)) to conduct sustained release of a chemotherapeutic agent. To confirm penetration of the agent into the HAb (2 cm3), an aqueous solution containing eosin dye was used at various vacuum pressures. To estimate the storage capacity of the HAb, blocks were weighed before and after being impregnated with the aqueous dye solutions, and the capacity of the block was calculated from the increase in weight after vacuum. In this slow-release study using vacuum, the anti-cancer drug methotrexate (MTX) was used in vitro. Four HAb (1 cm3) containing different concentrations of MTX, ranging from 1.22 to 2.38 mg per block, were studied. All were found to release the drug, maintaining a mean concentration of 0.22 to 0.32 microg/ml even after twelve days. This concentration is high enough to be effective against tumor cells. The results suggest that HAb impregnated with a chemotherapeutic agent using a simple vacuum system may serve as a valuable new method of administering local chemotherapy, primarily when used as a strut graft for bone defects. This new drug delivery system can also be used as an adjuvant material in extended curettage, which can also discourage recurrence of benign tumors without any risk of systemic toxicity.
ABSTRACT
A novel drug delivery system for osteomyelitis was developed in which a porous hydroxyapatite block (HAB) is loaded with antibiotic by a centrifugation method. In this study, implantation of HABs loaded with the aminoglycoside antibiotic, arbekacin, were tested in established Staphylococcus aureus osteomyelitis in the proximal tibia of rats after debridement of the marrow cavity. The animals were observed for radiographic signs of infection and tissue was examined histologically. The infections were also evaluated by bone cultures. Bacterial counts were statistically lower in rats implanted with an antibiotic-loaded HAB than in those given a drug-free HAB. Radiographical and histological observations also showed beneficial effects of the antibiotic-loaded implant. The results suggest that the centrifugation method for loading HABs provides a simple drug delivery system. These antibiotic-loaded HABs may be useful for filling grafts in osteomyelitis.
