Implant-directed Magnetic Drug Targeting: Antibiotic therapy of peri-implant infections

• Applicants: Dr. Nina Ehlert, since 5/2023; Dr. Jessica Meißner, since 10/2020; Privatdozentin Dr. Janin Reifenrath
• Subject Area: Veterinary Medical Science
• Term: since 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 280642759

Project aim is the targeted, time independent accumulation of agents on implant surfaces by magnetic nanoparticles using an external electromagnetic field and a magnetizable implant material. In recent years research on nanoparticles gained a lot of importance, especially regarding drug delivery. However, certain skepticism arose whether the different targeting mechanisms are really effective and finally transferable to the human organism. Accordingly, the question “Does nanomedicine have a delivery problem?” is currently discussed intensively. The applied project approaches the topic from a different point of view using physical interaction instead of biochemical targeting. First examinations could already show a partial accumulation of magnetic nanoparticles on an implant surface in vivo, even if not on a therapeutically sufficient scale. However, the results enabled to narrow down closely necessary next working points and still promise a successful transfer of the primary concept.The magnetic nanoporous silica nanoparticle (MNPSNPs) developed in the first period will be modified to that effect that their capture by the mononuclear phagocytic system (MPS) will be reduce significantly by firstly adapting the already used PEGylation. Additionally, other approaches will be tested like adding surface proteins (e.g. CD47). All adaptions aim to prolong essentially the blood half-life of the MNPSNPs. Furthermore, magnetic properties will be enhanced. On the one hand MNPSNPs will be again modified while maintaining their superparamagnetic behavior. On the other hand changes in design and material aim to improve the implant´s impact on the nanoparticle attraction. These adaptions will be tested in preliminary tests by a project partner who will then produce optimized implants for the planned working packages. Before transferring both – adapted MNPSNPs and implants – to in vivo trials, ex vivo examinations were performed using the isolated perfused sheep leg. Here, microdialysis is used to determine release kinetics of the linked antibiotics. Furthermore, accumulation of MNPSNPs on the implant will be assessed. After choosing the most suited MNPSNP and implant both components were tested for their effectiveness in an infection model using rats. The implants were fixed at the bone, orthotopic to the future application site, and fluorescent and antibiotic loaded MNPSNPs were administered systemically. Evaluation will include determination of localization by fluorescence microscopy and therapeutic impact on the infection by assessment of the biofilm on the implant surface.

• DFG Programme: Research Grants
• Ehemalige Antragsteller: Professor Dr. Peter Behrens, until 5/2023 (†); Professor Dr. Manfred Kietzmann, until 9/2020