The reaction of aqueous Zoledronate solutions with beta-tricalcium phosphate resulted in the precipitation of a crystalline Zoledronate complex on the surface of the calcium phosphate. This complex (CaNa[(HO)(C4H5N2)C(PO3)(PO3H)](2)center dot xH(2)O) was found to be metastable, leading to a pure calcium complex [Ca-3[(HO)(C4H5N2)C(PO3)(PO3H)(2)center dot xH(2)O] upon washing with water. This latter compound was found to release the bisphosphonate in phosphate buffers, in direct proportion to the phosphate concentration, while using a specific in vitro bone resorption model, an inhibition of osteoclastic activity was observed with this material. This suggested that when this composite is implanted in bone tissues, the drug will be released in greater concentration the more the bone is being resorbed, resulting in a decrease of osteoclast activity and making this drug device combination suitable for practical application as a bisphosphonate local delivery system. In addition, the chemical environment of the bisphosphonate moiety in the two reported bisphosphonate/calcium phosphate composites was probed using P-31 and Na-23 magic-angle-spinning NMR and two-dimensional P-31 homonuclear and P-31-H-1 heteronuclear correlation experiments, thus giving clear evidence that modem high-resolution solid-state NMR is a powerful tool for the characterization of calcium phosphate-based biomaterials.
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