Percutaneous devices—indwelling catheters—related infections are serious clinical incidents. It is accordingly necessary to develop anti-infective coating materials suitable for the devices for long-term effectiveness. In our research group, highly dispersible and crystalline hydroxyapatite (HAp) nanoparticles doped with metallic or halogen ions possessing antibacterial activities have been developed. In this study, antibacterial, dispersible, and crystalline zinc (Zn)-doped hydroxyapatite [Zn(15)-HAp] nanoparticles substituted with 13.5% Zn content [Zn/(Zn + Ca) × 100] were prepared by a wet chemical method using an anti-sintering agent through calcination. Antibacterial activities of Zn(15)-HAp nanoparticles were evaluated using Escherichia coli ( E. coli) and Staphylococcus aureus. The survival rates of the bacteria on Zn(15)-HAp nanoparticles were significantly lower than that on normal HAp (nHAp) coated surfaces, while no influences were observed on proliferation of L929 cells. Even after soaking Zn(15)-HAp nanoparticles in PBS for 2 weeks, the antibacterial activities against E. coli were maintained at a similar level to a 20 min soaking. The bacterial death was related to not only ion-exchange phenomenon between Zn and magnesium ions but also accumulation of reactive oxygen species (ROS) in the cells. Allergic-like reactions—anaphylactoid reactions—might not readily occur with Zn(15)-HAp nanoparticles because the amounts of histamine released from HMC-1 cells co-cultured with nanoparticles were not significantly different to that of nHAp, but were statistically much lower than that of chlorhexidine.
Background To prevent tunnel infection of indwelling catheters, impregnation with antiseptics or antibiotics is effective. However, 13 patients using chlorhexidine–silver sulfadiazine-impregnated catheters experienced serious anaphylactic shock in Japan. Thus, it is necessary to select a suitable evaluation method for allergic reactions and develop a novel antibacterial coating material that does not cause anaphylactic reaction. Methods Two types of highly dispersible and antibacterial nanoparticles—fluorine (F)-doped hydroxyapatite (HAp) and zinc (Zn)-doped HAp—were tested using of the system and compared with compound 48/80 (c48/80) as a histamine releaser and chlorhexidine gluconate (CHG) as an anaphylactic inducer. Results The histamine concentrations secreted from HMC-1 cells remained mostly the same even with the addition of F-HAp and Zn-HAp. On the contrary, the levels of the chemical mediators from the cells by the addition of F-HAp and Zn-HAp were significantly lower than those of only c48/80 and CHG without the addition of HAp. Conclusions The assay was a well-evaluated method for quantifying histamine concentrations released from HMC-1 cells. Our study induced HMC-1 cells accompanied with and without the nanomaterials; the potential of F-HAp and Zn-HAp to induce allergic reactions was found to be quite low. Therefore, the antibacterial nanomaterials are expected to hardly induce anaphylactoid reactions.
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