Apatitic bone cements have been used as a clinical bone substitutes and drug delivery vehicles for therapeutic agents in orthopedic applications. This has led to their combination with different drugs with known ability to foster bone formation. Recent studies have evaluated Simvastatin for its role in enhanced bone regeneration, but its lipophilicity hampers incorporation and release to and from the bone graft. In this study, injectable calcium phosphate foams (i-CPF) based on α-tricalcium phosphate were loaded for the first time with Pitavastatin. The stability of the drug in different conditions relevant to this study, the effect of the drug on the i-CPFs properties, the release profile, and the in vitro biological performance with regard to mineralization and vascularization were investigated. Pitavastatin did not cause any changes in neither the micro nor the macro structure of the i-CPFs, which retained their biomimetic features. PITA-loaded i-CPFs showed a dose-dependent drug release, with early stage release kinetics clearly affected by the evolving microstructure due to the setting of cement. in vitro studies showed dose-dependent enhancement of mineralization and vascularization. Our findings contribute towards the design of controlled release with low drug dosing bone grafts: i-CPFs loaded with PITA as osteogenic and angiogenic agent.
Biomimetic Materials/chemistry , Bone Substitutes/chemistry , Calcium Phosphates/chemistry , Quinolines/chemistry , Bone Cements/chemistry , Bone Substitutes/metabolism , Bone Substitutes/pharmacology , Bone Transplantation , Compressive Strength , Drug Liberation , Endothelial Progenitor Cells/metabolism , Humans , Injections , Mechanical Tests , Mesenchymal Stem Cells/metabolism , Osteogenesis , Quinolines/metabolism , Quinolines/pharmacology , Simvastatin/chemistry , Simvastatin/standards , X-Ray Microtomography
Silver nanoparticles (Ag-NPs) are used in a wide variety of products, prompting concerns regarding their potential environmental impacts. To accurately determine the toxicity of Ag-NPs it is necessary to differentiate between the toxicity of the nanoparticles themselves and the toxicity of ionic silver (Ag) released from them. This is not a trivial task given the reactive nature of Ag in solution, and its propensity for both adsorption and photoreduction. In the experiments reported here, we quantified the loss of silver from test solutions during standard ecotoxicity testing conducted using a variety of different test container materials and geometries. This sensitive (110m)Ag isotope tracing method revealed a substantial underestimation of the toxicity of dissolved Ag to the green algae Pseudokirchneriella subcapitata when calculated only on the basis of the initial test concentrations. Furthermore, experiments with surface-functionalized Ag-NPs under standard algal growth inhibition test conditions also demonstrated extensive losses of Ag-NPs from the solution due to adsorption to the container walls, and the extent of loss was dependent on Ag-NP surface-functionality. These results hold important messages for researchers engaged in both environmental and human nanotoxicology testing, not only for Ag-NPs but also for other NPs with various tailored surface chemistries, where these phenomena are recognized but are also frequently disregarded in the experimental design and reporting.
Adsorption , Ecotoxicology/methods , Nanoparticles/toxicity , Silver/toxicity , Toxicity Tests/methods , Chlorophyta/drug effects , Drug Packaging , Humans , Ions/toxicity , Nanoparticles/chemistry , Silver/chemistry
