Ex vivo alendronate localization at the mesoporous titania implant/bone interface

An attractive approach in implant technology is local drug delivery, and design of efficient, safe and reliable treatments. Our hitherto strategy has been to coat Ti implants with a thin mesoporous TiO2 film that in turn is loaded with an osteoporosis drug, such as Alendronate (ALN) that is known to suppress osteoclastic activity. This system has proven highly successful and results in excellent osseointegration. However, more detailed information about drug-release and distribution at the bone/implant interface is needed. In this study, C-14-ALN loaded titanium implants were placed up to 8 weeks into rat tibia and the spatial-temporal distribution of the drug was evaluated. Autoradiography data demonstrated a sustained release of C-14-ALN and the released drug remained bound to bone in close vicinity, within 500 micrometers, of the implants. Liquid scintillation counting experiments confirmed that the distal transport of released C-14-ALN was extremely low. The results are favorable as they show that ALN stays for a long time in the vicinity of the implant and may therefore improve for a long time the mechanical fixation of bone anchored implants. Moreover, these findings suggest due to the low systemic spreading a minimal risk of Alendronate related systemic side effects.