Time Course of Zoledronate Interaction with Hydroxyapatite Nanocrystals

Zoledronate-modified hydroxyapatite nanocrystals (HAZOL) can be successfully obtained through direct synthesis in aqueous solution in spite of the great affinity of this bisphosphonate for calcium ions, which should promote the precipitation of calcium zoledronate. This study investigates the time course of the reaction in order to clarify the peculiar interaction of zoledronate (ZOL) with hydroxyapatite (HA). The results demonstrate that the first precipitate during the direct synthesis of HAZOL is indeed constituted of a relevant amount of amorphous calcium zoledronate together with small nanocrystals; however, the relative amount of crystalline material increases at the expenses of the amorphous phase during the time course of the reaction. The final HAZOL nanocrystals are smaller and display reduced lengths of the coherently scattering domains with respect to the control hydroxyapatite nanocrystals. Zoledronate incorporation, which can be detected also through Raman spectroscopy, amounts to 7.4 wt %, and it provokes a reduction of zeta potential. The suitable coordination geometry of Ca atoms in HA justifies the high affinity of the bisphosphonate for hydroxyapatite structure, which leads to ZOL inclusion between the coherently scattering domains during HA crystal growth. At variance, zoledronate chemisorption on preformed HA nanocrystals increases up to 3.3 wt % without causing appreciable morphological and structural modifications.