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    An evaluation of colloidal and crystalline properties of CaCO3 nanoparticles for biological applications
    Biodegradable calcium carbonate carriers are a promising and safe nanoparticle platform which might enable various applications as an engineered nanomaterial in health care, food and cosmetics. However, engineered nanoparticles can exhibit new forms of toxicity that must be carefully evaluated before being widely adopted in consumer products or novel drug delivery systems. To this end, we studied four common calcium carbonate particle systems (calcite nanoparticles, amorphous sub-micrometer and vaterite sub-micrometer and micrometer particles) and compared their behavior in biological medium and in cell culture experiments. The thermodynamically stable calcite phase is shown to maintain its morphological features as no phase transformation occurs. Size- and time-dependent phase transformation of the less stable vaterite particles are observed within 96h in cell medium. The protein serum albumin can be an effective inhibitor of phase-transition and it is shown to improve colloidal stability. The impact of the biological environment goes beyond protein-corona formation, as we observed rapid dissolution of amorphous particles in high ionic strength cell medium, but not in Millipore water. Cellular responses of human osteoblasts against CaCO3 particles indicate that increased intracellular calcium ions improve viability and that particle internalization is not size-dependent. Useful insights for designing CaCO3-based delivery systems are provided and also corroborate to the idea that intrinsic material properties as well as environmental conditions are of relevance for the successful implementation of dispersed CaCO3 particles in drug delivery systems and in other applications.
    Wissenschaftlicher Artikel
    Band:
      103  204
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    Co-delivery of cisplatin and doxorubicin from calcium phosphate beads / matrix scaffolds for osteosarcoma therapy
    Bone substitute materials with a controlled drug release ability can fill cavities caused by the resection of bone tumours and thereby combat any leftover bone cancer cells. The combined release of different cytostatics seems to enhance their toxicity. In this study, calcium phosphate beads and matrix scaffolds are combined for a long-term co-delivery of cis-diamminedichloroplatinum (cisplatin, CDDP) and doxorubicin hydrochloride (DOX) as clinical relevant model drugs. Tricalcium phosphate/alginate beads as additional drug carrier are produced by droplet extrusion with ionotropic gelation and incorporated in scaffold matrix by freeze gelation without sintering. CDDP shows a short burst release while DOX has a continuous release measurable over the entire study period of 40days. Drug release from matrix is decreased by ~30% compared to release from beads. Nevertheless, all formulations follow the Korsmeyer-Peppas release kinetic model and show Fickian diffusion. Cytotoxic activity was conducted on MG-63 osteosarcoma cells after 1, 4, and 7days with WST-1 cell viability assay. Co-loaded composites enhance activity towards MG-63 cells up to ~75% toxicity while reducing the released drug quantity. The results suggest that co-loaded beads/matrix scaffolds are highly promising for osteosarcoma therapy due to synergistic effects over a long period of more than a month.
    Wissenschaftlicher Artikel
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      99  125
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    Combined effect of magnesia and zirconia on the bioactivity of calcium silicate ceramics at C\S ratio less than unity
    This paper describes the effect of magnesia in the presence of zirconia on the bioactivity, microstructure and physico-mechanical properties of calcium silicate composition adjusted at calcia/silica ratio(C/S) of 0.5. A mixture from calcium carbonate and silica was conducted at C/S of 0.5. 20wt.% of magnesia and 5-25wt.% of ZrO2 were added. Each mixture was mixed with ethanol in a planetary ball mill, dried, formed and fired at a temperature of 1325±5°C. Phase composition, FE-SEM, and physico-mechanical properties of the fired specimens were determined and explained. The in vitro bioactivities of these specimens were investigated by analysis of their abilities to form apatite in the simulated body fluid (SBF) for a short time (7days) using SEM-EDS. The findings indicated that the surface of the specimens containing 5 and 15wt.% ZrO2 were completely covered by single and multilayered hydroxyapatite (HA) precipitate typical to "cauliflower" morphology, respectively. The surface of the specimen containing 25wt.% ZrO2 did not cover, but there are some scattered HA precipitate. The differences among the results were rationalized based on the phase composition. Vickers hardness and fracture toughness of the specimens of highly promised bioactivity were 2.32-2.57GPa and 1.80-1.50MPa. m1/2, respectively. The properties of these specimens are similar to the properties of human cortical bone. Consequently, these composites might be used as bone implant materials.
    Wissenschaftlicher Artikel
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      111  77
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    Multi-loaded ceramic beads/matrix scaffolds obtained by combining ionotropic and freeze gelation for sustained and tuneable vancomycin release
    For a targeted release against bacteria-associated bone diseases (osteomyelitis) ceramic beads with a high drug loading capacity, loaded with vancomycin as model antibiotic, are synthesized as drug carrier and successfully incorporated in an open porous hydroxyapatite matrix scaffold via freeze gelation to prevent bead migration at the implantation site and to extend drug release. We demonstrate that the quantity of loaded drug by the hydroxyapatite and β-tricalcium phosphate beads, produced by ionotropic gelation, as well as drug release can be tuned and controlled by the selected calcium phosphate powder, sintering temperature, and high initial vancomycin concentrations (100mg/ml) used for loading. Bead pore volume up to 68mm(3)/g, with sufficiently large open pores (pore size of up to 650nm with open porosity of 72%) and high surface area (91m(2)/g) account likewise for a maximum drug loading of 236mg/g beads or 26mg/sample. Multi-drug loading of the beads/matrix composite can further increase the maximum loadable amount of vancomycin to 37mg/sample and prolong release and antibacterial activity on Bacillus subtilis up to 5days. The results confirmed that our approach to incorporate ceramic beads as drug carrier for highly increased drug load in freeze-gelated matrix scaffolds is feasible and may lead to a sustained drug release and antibacterial activity.
    Wissenschaftlicher Artikel
    Band:
      122  151