Loading and release of doxycycline hyclate from strontium-substituted calcium phosphate cement.

Novel Sr-substituted calcium phosphate cement (CPC) loaded with doxycycline hyclate (DOXY-h) was employed to elucidate the effect of strontium substitution on antibiotic delivery. The cement was prepared using as reactants Sr-substituted beta-tricalcium phosphate (Sr-beta-TCP) and acidic monocalcium phosphate monohydrate. Two different methods were used to load DOXY-h: (i) the adsorption on CPC by incubating the set cement in drug-containing solutions; and (ii) the use of antibiotic solution as the cement liquid phase. The results revealed that the Sr-substituted cement efficiently adsorbs the antibiotic, which is attributed to an enhanced accessibility to the drug-binding sites within this CPC. DOXY-h desorption is influenced by the initial adsorbed amount and the cement matrix type. Furthermore, the fraction of drug released from CPCs set with DOXY-h solution was higher, and the release rate was faster for the CPC prepared with 26.7% Sr-beta-TCP. The analysis of releasing profiles points to Fickian diffusion as the mechanism responsible for antibiotic delivery. We can conclude that Sr substitution in secondary calcium phosphate cements improves their efficiency for DOXY-h adsorption and release. The antibiotic loading method provides a way to switch from rapid and complete to slower and prolonged drug release.

Combined effect of strontium and pyrophosphate on the properties of brushite cements.

In this study we report the synthesis of strontium-containing brushite cement with good cohesion and a diametral tensile strength (DTS) of 5 MPa. The cement powder, composed of beta-tricalcium phosphate (beta-TCP) and monocalcium phosphate, was adjusted by different concentrations of strontium and pyrophosphate ions. The cement liquid phase was 2M phosphoric acid solution. The cement cohesion and mechanical properties were measured after being aged in water for 24h at 37 degrees C. It was found that at low concentration both strontium and pyrophosphate ions inhibit the cement setting reaction. However, the final setting time was significantly reduced when SrCl2 increased from 5 to 10 wt.% at pyrophosphate concentrations equal to or higher than 2.16 wt.%. The incorporation of strontium ions did not increase the DTS of brushite cements significantly. In contrast, the addition of pyrophosphate ions did increase the DTS of brushite cements significantly. When both ions were added simultaneously, the brushite cement with a Sr2+ content of 5 wt.% had the highest DTS value. Nevertheless, the DTS values of Sr-containing cements were significantly reduced if the pyrophosphate concentration was higher than 2.16 wt.%. The Sr2+ ions had a negative effect on brushite cement cohesion, although the solid weight loss started to decrease at Sr2+ concentrations higher than 5 wt.%.

Beta-tricalcium phosphate release from brushite cement surface.

Different in vivo studies demonstrated that brushite cements are biocompatible, bioresorbable, and osteoconductive. However, the decay of brushite cements has been scarcely studied even though it may be of great concern for clinical applications in highly blood-perfused regions. This work was elaborated to elucidate factors that determine brushite cement surface disintegration. For that, brushite cements were modified using in their preparation different aqueous solutions of phosphoric, glycolic, tartaric, and citric acids in concentrations that were reported to improve the cement properties. Two-viscosity enhancing polysaccharides, chondroitin-4 sulfate and hyaluronic acid, were also assayed. Thereafter, pre- and set cement samples were immersed in distilled water for 24 h. The cement-solid weight loss, microstructure, liquid phase viscosity, mean size of the released particles, and zeta potential were analyzed using X-ray diffraction, FTIR spectroscopy, light scattering, scanning electron microscopy and optical microscopy. It was found that the particles released from the cement surface were beta-TCP, and their amount depends on the carboxylic acid used in the preparation of the cement. The addition of hyaluronic acid and chondroitin-4 sulfate decreased the amount of released particles from the surface of the set brushite cement made with citric acid. Furthermore, the hyaluronic acid increased significantly the viscosity of the citric acid solution and the cement paste prepared with this liquid phase showed a pronounced step down in particle release. In this study, we showed that the water solubility of calcium carboxylate and the viscosity of mixing liquid may dictate the superficial disintegration of brushite cements.

Vertical bone augmentation with granulated brushite cement set in glycolic acid.

Brushite cements are a biocompatible materials that are resorbed in vivo. A new cement composed of a mixture of monocalcium phosphate (MCP) and beta-tricalcium phosphate (beta-TCP) that sets using glycolic acid (GA) was synthesized and characterized. After setting, the cement composition, derived from X-ray diffraction, was 83 wt % brushite and 17 wt % beta-TCP with an average brushite crystal size of about 2.6 +/- 1.4 microm. The cement has a diametral tensile strength of 2.9 +/- 0.7 MPa. Granules prepared from the set-cement were used as grafting material in bone defects on rabbit calvaria for evaluating in vivo its bone regeneration capacity. Considerable cement resorption, improvement in the bone mineral density, and bone neoformation was observed after 4 weeks of the granules' implantation.