Reaction of Zoledronate with β-Tricalcium Phosphate for the Design of Potential Drug Device Combined Systems

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• 作者：H&#xe9 ; l&#xe8 ; ne Roussi&#xe8 ; re ; Franck Fayon ; Bruno Alonso ; Thierry Rouillon ; Verena Schnitzler ; Elise Verron ; J&#xe9 ; rô ; me Guicheux ; Marc Petit ; Dominique Massiot ; Pascal Janvier ; Jean-Michel Bo
• 刊名：Chemistry of Materials
• 出版年：2008
• 出版时间：January 8, 2008
• 年：2008
• 卷：20
• 期：1
• 页码：182 - 191
• 全文大小：732K
• 年卷期：v.20,no.1(January 8, 2008)
• ISSN：1520-5002

文摘

The reaction of aqueous Zoledronate solutions with β-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)]·xH₂O) was found to be metastable, leading to a pure calcium complex [Ca₃[(HO)(C₄H₅N₂)C(PO₃)(PO₃H)]₂·xH₂O] 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 ³¹P and ²³Na magic-angle-spinning NMR and two-dimensional ³¹P homonuclear and ³¹P−¹H heteronuclear correlation experiments, thus giving clear evidence that modern high-resolution solid-state NMR is a powerful tool for the characterization of calcium phosphate-based biomaterials.