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Novel biomaterials for bisphosphonate delivery.

Josse S, Faucheux C, Soueidan A, Grimandi G, Massiot D, Alonso B, Janvier P, Laïb S, Pilet P, Gauthier O, Daculsi G, Guicheux JJ, Bujoli B, Bouler JM

Faculté des Sciences et des Techniques, Laboratoire de Synthèse Organique, University of Nantes, UMR CNRS 6513 and FR CNRS 2465, 2 Rue de la Houssinière , BP92208, 44322 Nantes Cedex 3, France.

One type of gem-bisphosphonate (Zoledronate) has been chemically associated onto calcium phosphate (CaP) compounds of various compositions. For that purpose, CaP powders of controlled granulometry have been suspended in aqueous Zoledronate solutions of variable concentrations. Using mainly (31)P NMR spectroscopy, two different association modes have been observed, according to the nature of the CaP support and/or the initial concentration of the Zoledronate solution. beta-tricalcium phosphate (beta-TCP) and mixtures of hydroxyapatite and beta-TCP (BCPs) appear to promote Zoledronate-containing crystals formation. On the other hand, at concentrations <0.05 mol l(-1) CDAs (calcium deficients apatites) seem to undergo chemisorption of the drug through a surface adsorption process, due to PO(3) for PO(4) exchange, that is well described by Freundlich equations. At concentrations >0.05 mol l(-1), crystalline needles of a Zoledronate complex form onto the CDAs surface. The ability of such materials to release Zoledronate, resulting in the inhibition of osteoclastic activity, was shown using a specific in vitro bone resorption model.

Published 3 December 2004 in Biomaterials, 26(14): 2073-80.
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