Continuous antimicrobial mechanism of dispersible hydroxyapatite nanoparticles doped with zinc ions for percutaneous device coatings

Abstract

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.