Sequential drug release of self-ordered titania nanotubes with antibacterial function and anticancer ability for bone cancer treatments.

The success of tumor prosthesis relies on the preclusion of deep infection and local recurrence in limb sparing surgery. The orthopedic implants enabling to simultaneously possess the antibacterial function and anticancer ability have become a desirable local therapy in the treatment of bone cancer. In this regard, we proposed a promising concept of the sequential release in a dual-drug system by combing titania nanotubes and chitosan as drug nanoreservoirs and sustained release films, respectively. An electrochemical anodization technique, controlled by anodization voltage, electrolyte composition, and processing time, was used to fabricate self-ordered titania nanotubes on the titanium surface, with their lengths simply tuned by the processing time, for drug loading. Two drugs of cisplatin and vancomycin as model anticancer and antibiotic, respectively, were sequentially loaded in nanotubes to investigate the release kinetics. The release profiles of cisplatin and vancomycin were found to be related to the spatial positioning of each drug on the nanotubes. Such a release sequence can be attributed to the anisotropic diffusion of drugs from the nanotubes, which can be further sustained for over 4 weeks through chitosan coverage. The drug release behavior was first evaluated in water using ultraviolet-visible spectroscopy for the quantitative analysis of release kinetics over time. The influence of dual-drug-loaded nanotubes on the growth ofStaphylococcus aureusand osteogenic sarcomain vitrowas systematically evaluated for the therapeutic efficacy of bone cancer treatment. A high correlation between the viabilities of bacteria and cells and dual-drug release profiles was observed, indicating the feasibility of our nanotube-based concept utilizing a sequential release pattern to combat initial bacterial infection and prevent local recurrence.