Experimental research on the local delivery of adriamycin incorporated into hydroxyapatite beads

Various forms of hydroxyapatite(HAP) materials have been extensively developed for orthopedic and dental applications as bone grafts and bone substitutes. It seems useful to incorporate cancer chemotherapeutic agents into implant materials used in the sites of the bony defect postoperation of bone tumors, to control local recurrence. This study was conducted to investigate whether porous HAP is appropriate as a drug carrier for adriamycin(ADR) by determining the anticancer effects of ADR-HAP beads and release behavior of ADR from HAP beads. Porous HAP bead (8.48 mm in diameter, 531±0.7 mg in weight) was used as a model material, Various ADR-HAP beads(ADR 0.4∼6.0 mg/bead) were implanted s. c. into Sprague-Dawley rats at 6 day postinoculation of Swarm rat chondrosarcoma. ADR levels were determined using HPLC. ADR in the tumors released from ADR-HAP beads(6.0 mg/bead) were observed over a 13-week period. However, the diffusion of the drug to other organs such as heart and liver was very low compared with the level in the tumors. ADR HAP beads more than the dose of 1.0 mg/bead showed strong antitumor activities with dose of ADR. The dose of 6.0 mg/bead showed most efficacy, and no toxic death caused, which 98% growth inhibition on Day 31, and the survival advantage of 339% increase in life span were obtained. HAP is thus concluded to be usable not only as a bone graft but as an anticancer drug carrier for achieving high sustained local levels of the anticancer drug in the implanted site, together a low systemic level.