Novel pH-responsive tobramycin-embedded micelles in nanostructured multilayer-coatings of chitosan/heparin with efficient and sustained antibacterial properties.

To endow orthopaedic implants with satisfactory antibacterial properties, the design and development of antibiotic coating on the surface of implants is highly desired. In this work a novel and facile strategy was developed to form pH-responsive layer-by-layer (LbL) films implanted with polymeric micelles as nano-vehicles loaded with charge-weak antibiotic drugs, enabling high drug loading efficiency. Negatively charged tobramycin (Tob)-embeded heparin miscells (HET) and positively charged chitosan (CHT) were exploited as a pH-responsive LBL multilayer building block, respectively. The formation mechanism and pH-stimulated release behavior of the Tob-contained heparin micelles were studied. The characterization on the morphologies, chemical compositions and hydrophilicity of the modified surface confirmed the successuful deposition of the Tob-loaded CHT/HET multilayers coatings on the polydopamine-modified Ti surface. The drug release profiles displayed fast release at pH 7.4 and slow release after exposure to weakly acidic environments. Antibacterial tests indicated that the Tob-embed CHT/HET nanostructured multilayers not only strongly inhibited initial bacterial adhesion, but also disruptted biofilm formation. Particularly, this functional coatings showed "long-term antibacterial" pattern in acid condition. Meanwhile, MC3T3 cells showed acceptable adhesion, spread and proliferation on the multilayer coatings in cytocompatible studies. In a word, these multilayer coatings incorporated with a wide variety of antibiotics show promisiong applications in preventing postoperative infection and resolving unmet clinical need.