134. Fonctionnalisation de l’hydroxyapatite avec la cyclodextrine pour le relargage continu d’agents thérapeutiques. - Functionnalisation of hydroxyapatite with cyclodextrine for the sustained release of therapeutic agents.

B. Martel, S. Leprêtre, F Chai, J.C. Hornez, G. Vermet, N. Tabary, M. Descamps, N. Blanchemain, M. Morcellet, H.F. Hildebrand (Lille, France)

Bone diseases, as cancer, osteomyelitis or traumatism can lead to the substitution of the unhealthy bone by a biomaterial ceramic, which is often hydroxyapatite (HA), mineral component of the bone. These grafts are often followed by a heavy systemic treatment to avoid new infection or a relapse, because of the low flux renewal. In the present work, we propose a new way of functionalization of HA with cyclodextrins (CDs) in order to improve its sorption capacity towards antibiotics, and to provoke their in situ prolonged release.
The immobilization of CDs on hydroxyapatite was achieved by using polycarboxylic acids (citric, polyacrylic and 1,2,3,4-butanetetracarboxylic acids) as crosslinking agents[1]. Porous supports were impregnated by the reactants and treated under various heating conditions. After washings, the crosslinked polymer formed between CD and crosslinking agents in the pores of hydroxyapatite was observed by MEB, IRTF and TGA. In vitro releases profiles of ciprofloxacin were performed in order to evaluate the efficiency of the functionalization. Proliferation and cytotoxicity tests were carried out to observe the biocompatibility of the modified HA. Finally, samples were impregnated with ciprofloxacin whose release profile was observed by spectrophotometry in water batch.

The different characterization experiments showed a deposition of about 5%-wt of CD polymer on hydroxyapatite samples. Temperature and time of heating treatment allowed controlling the amount of fixed CD polymer. Biological tests showed the biocompatibility of the samples, and release kinetics profiles obtained from virgin and grafted samples were far different.

[1] B. Martel, N. Blanchemain, F. Boschin, S. Haulon, E. Delcourt-Debruyne, H.F. Hildebrand et M. Morcellet. Patent appl. PCT/FR2005/002829 (2005), WO 2006/051227 (2006), JPN:: 2007-540685 (2007), CN101080247A (2007)

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