Electrolytic deposition of calcium etidronate drug coating on titanium substrate

Wear debris-induced osteolysis is the major cause of aseptic loosening and failure of hip implants. One of the promising therapeutic interventions to improve the longevity of hip implants is to administrate bisphosphonate drug to inhibit osteoclastic bone resorption. This study aimed at developing new techniques of directly combining bisphosphonate with implants to achieve local delivery and controlled release of the drug. Instead of using soluble sodium salt, we proposed to apply sparingly soluble calcium salt of bisphosphonate as a potential long-term antiosteolysis coating on hip implants. Calcium salt of etidronate, a member of the bisphosphonate family of potent osteoclast inhibitors, was used in this pilot study. By adopting the electrolytic deposition (ELD) technique, which was developed for ceramic coatings including calcium phosphates, we demonstrated that a thin layer of calcium bisphosphonate could be deposited onto titanium surface. The drug coating is amorphous as characterized with X-ray diffraction, and has globular morphology under the scanning electron microscope. Electrospray-ionization mass-spectrometry (ESI-MS) and Fourier-transformed infrared spectroscopy confirmed that the molecular structure of the etidronate (m/z 205, H3L-, the single dissociated form of parent etidronic acid, denoted as H4L) was preserved after the ELD process. In vitro release into a "physiological" buffer solution confirmed that the etidronate concentration was limited by its low solubility. The etidronate concentration was 8 x 10(-5) M at day 1 and kept relatively stable at approximately 6 x 10(-5) M from day 2 to day 8. The deposition mechanisms of the drug coating and its potential efficacy as an antiosteolytic release source were discussed.