Allal Barroug

Nuclear Magnetic Resonance Spin‐Spin Relaxation of the Crystals of Bone, Dental Enamel, and Synthetic Hydroxyapatites

Studies of the apatitic crystals of bone and enamel by a variety of spectroscopic techniques have established clearly that their chemical composition, short‐range order, and physical chemical reactivity are distinctly different from those of pure hydroxyapatite. Moreover, these characteristics change with aging and maturation of the bone and enamel crystals. Phosphorus‐31 solid state nuclear magnetic resonance (NMR) spin‐spin relaxation studies were carried out on bovine bone and dental enamel crystals of different ages and the data were compared with those obtained from pure and carbonated hydroxyapatites. By measuring the31P Hahn spin echo amplitude as a function of echo time, Van Vleck second moments (expansion coefficients describing the homonuclear dipolar line shape) were obtained and analyzed in terms of the number density of phosphorus nuclei.31P magnetization prepared by a 90° pulse or by proton‐phosphorus cross‐polarization (CP) yielded different second moments and experienced different degrees of proton spin‐spin coupling, suggesting that these two preparation methods sample different regions, possibly the interior and the surface, respectively, of bone mineral crystals. Distinct differences were found between the biological apatites and the synthetic hydroxyapatites and as a function of the age and maturity of the biological apatites. The data provide evidence that a significant fraction of the protonated phosphates (HPO4−2) are located on the surfaces of the biological crystals, and the concentration of unprotonated phosphates (PO4−3) within the apatitic lattice is elevated with respect to the surface. The total concentration of the surface HPO4−2 groups is higher in the younger, less mature biological crystals.

Infrared, Raman and NMR investigations of risedronate adsorption on nanocrystalline apatites

The aim of the current work was to study the physico-chemical interactions of a bisphosphonate molecule, risedronate, with a well-characterised synthetic nanocrystalline apatite (NCA) as a model bone mineral. We adopted a global approach, using complementary physico-chemical techniques such as FTIR, RAMAN and NMR spectroscopies in order to learn more about the interaction process of risedronate with the apatitic surface. The results obtained suggest that risedronate adsorption corresponds to an ion substitution reaction with phosphate ions occurring at the crystal surface. This mechanism explains the greater amount adsorbed (N) for NCA, compared to well crystallised stoichiometric hydroxyapatite, attributable to the well-developed hydrated layer at the surface of the nanocrystals. However, most calcium ions remain attached to the solid phase and the formation of insoluble risedronate calcium salts must also be considered as a competitive reaction to the adsorption. Thus a calcium risedronate salt was synthesised and fully characterised for comparison to the solids after adsorption. Following spectroscopic results, it can be concluded that a strong interaction was established between risedronate ions and calcium ions at the apatitic surface. However, under these experimental conditions there is no nucleation of a distinct calcium risedronate salt and the apatite crystals retain their integrity.

Adsorption on apatitic calcium phosphates for drug delivery: interaction with bisphosphonate molecules

Bisphosphonates (BPs) are well established as an important class of drugs for the treatment and prevention of several bone disorders including osteoporosis. This work investigated the interaction of two bisphosphonates, risedronate and tiludronate, with several apatitic supports, a well-crystallised hydroxyapatite (HA) and nanocrystalline apatites with varying maturation times, chemical composition and surface characteristics. The purpose was to fully understand the adsorption mechanism and desorption process, by the evaluation of the effect of several physicochemical parameters (temperature, pH and concentration of calcium and phosphate ions). Whatever the nature of the BP and the structure and composition of the apatite, the adsorption of such anti-resorptive agents can be well described as an ion exchange-reaction between phosphates species on the apatitic surface and BP molecules in solution. However, the parameters of adsorption can vary depending on the physicochemical conditions of the adsorption reaction. In addition, the structure and composition of the apatitic surface also influence the adsorption properties. Finally, BPs molecules are slowly released from apatitic supports, because most of the adsorbed molecules are irreversibly bound and not spontaneously released by dilution or simple washing. Moreover, similar to their adsorption, the release of bisphosphonates is strongly affected not only by the chemical properties of the molecule, but also by the chemical and structural characteristics of the apatitic substrates. The understanding of the adsorption and release processes provides fundamental tools for the development of drug delivery systems using apatite materials.

Exchange Reactions at Calcium Phosphates Surface and Applications to Biomaterials

The interaction of calcium phosphates with biological molecules under controlled conditions permits the formulation of meaningful conclusions concerning the driving forces. The uptake and release at the material-solution interface is the result of the various interactions between and within the system components which include the solid surface, the adsorbate, the solvent and other solutes present. The understanding of adsorption and desorption mechanisms with respect to active molecules can be exploited for the development of drug delivery applications.

Injectability, microstructure and release properties of sodium fusidate-loaded apatitic cement as a local drug-delivery system

The introduction of an antibiotic, sodium fusidate (SF), into the liquid phase of calcium carbonate-calcium phosphate (CaCO3-CaP) bone cement was evaluated, considering the effect of the liquid to powder ratio (L/P) on the composition and microstructure of the set cement and the injectability of the paste. In all cases, we obtained set cements composed mainly of biomimetic carbonated apatite analogous to bone mineral. With this study, we evi-denced a synergistic effect of the L/P ratio and SF presence on the injectability (i.e., the filter-pressing pheno-menon was suppressed) and the setting time of the SF-loaded cement paste compared to reference cement (without SF). In addition, the in vitro study of SF release, according to the European Pharmacopoeia recommendations, showed that, regardless of the L/P ratio, the cement allowed a sustained release of the antibiotic over 1month in sodium chloride isotonic solution at 37°C and pH7.4; this release is discussed considering the microstructure characteristics of SF-loaded cements (i.e., porosity, pore-size distribution) before and after the release test. Finally, modelling antibiotic release kinetics with several models indicated that the SF release was controlled by a diffusion mechanism.