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

Abstract

The treatment of implant-associated infections is still a major topic in medical-related research. In addition to classical systemic therapy, many approaches enable local treatment at the infection site. Porous silica nanoparticles are particularly interesting here, as they can be loaded with antibacterial drugs. Combining these porous silica nanoparticles with a magnetic iron oxide core to a core-shell particle provides an even more sophisticated drug-delivery system, as hyperthermia or a directed concentration at the desired tissue by a magnetic field is possible. However, the profile often displays a burst release of the incorporated drug directly when the nanoparticles are exposed to physiological media. This uncontrolled release at non-targeted tissue is unsuitable for applications in implant-associated infection treatment because the drug concentration in the infected tissue will stay relatively low. A polymer shell can provide an elegant solution, as it can block the pore, preventing an early release of the drug. If a pH-responsive polymer is chosen, the pH change at the infected implant can trigger the release precisely. In this study, we present core-shell-shell nanocarriers made of magnetic nanoporous silica nanoparticles, which are functionalized with a pH-responsive polymer for the pH-triggered delivery of the antibiotic enrofloxacin. We further solved the problem of a poorly stable dispersion of the polymer-functionalized particles in physiological media by adding a sulfonic acid modification.