Stimuli-responsive core-shell-shell nanocarriers for implant-directed magnetic drug targeting.

The treatment of implant-associated infections is still a major topic in medical-related research. As an evolution of classical systemic therapy, many approaches target local treatment at the infection site. Here, we present an innovative material approach to overcome the challenges of this local drug delivery. As an effective nanocarrier, we chose nanoporous silica, which fulfills the need for a high capacity to load antibacterial drugs. Combined with a magnetic iron oxide core, these core-shell particles provide a sophisticated drug-delivery system that allows targeted drug delivery to the desired tissue a magnetic field. However, the release profile often reveals the problem of an uncontrolled burst release of the incorporated drug in physiological media, leading to the loss of the cargo to the site of infection and resulting in an ineffective treatment of implant-associated infection. A pH-responsive polymer shell can provide an elegant solution, as the acidic pH occurring during an infection (pH 5-6) can trigger the release precisely, preventing an early release of the drug. In this study, we selected poly(2-(diethylamino)ethyl methacrylate) (PDEMA) with a perfect fitting isoelectric point of 6.7 for the establishment of a pH-responsive polymer shell. Furthermore, we addressed the issue of a poorly stable dispersion of particles functionalized with hydrophobic polymers in physiological media by adding a sulfonic acid modification to the inner pore surface of the nanoparticles. This modification influenced the amount of attached polymer and the drug release profiles. It was also useful to increase the incorporated amount of enrofloxacin. In summary, we present innovative and effective core-shell-shell nanocarriers based on magnetic nanoporous silica nanoparticles functionalized with a pH-responsive polymer for the pH-triggered delivery of the antibiotic enrofloxacin and suitable for targeting using a magnetic field.