Implant-directed Magnetic Drug Targeting: Antibiotic therapy of peri-implant infections
Final Report Abstract
The aim of the project was the targeted, time-independent enrichment of active substances on implant surfaces by magnetic nanoparticles using an external electromagnetic field and a magnetisable implant material. The novelty of the project was that the targeting of the nanoparticles was not to take place via biochemical recognition, but via a physical interaction. In the first funding period, partial accumulation of the nanoparticles in vivo on an implant was already achieved, although not yet to a therapeutically effective extent. In the second funding period, the developed magnetic nanoporous silica nanoparticles (MNPSNP) were combined with the surface protein CD47 to prevent them from being intercepted by the mononuclear phagocyte system (MPS) in order to increase the circulation time in the blood significantly. Furthermore, work was carried out on improving the magnetic properties of the MNPSNP, but also on adapting the implant design to a uniform magnetic field effect. Modified implants were produced by a project partner and analysed concerning their superparamagnetic properties. Both optimised components were transferred to the animal model via the intermediate step of an ex vivo model. The release of the coupled antibiotics and the accumulation of MNPSNP on the implants were measured using microdialysis tests on the isolated perfused sheep's leg. Implant design, MNPSNP and their release systems and model systems were adapted successfully and offer promising opportunities for the future. MNPSNP accumulation still remained insufficient. However, the results achieved provide new opportunities for the development of new approaches in the therapy of implant-associated infections.
Publications
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Biocompatibility and biodistribution of magnetic silica nanoparticles for implant directed magnetic drug targeting, EORS, September 2018, Galway, Irland (Vortrag)
Angrisani N.; Janssen H. C.; Kietzmann M.; Dahlhaus D.; Warwas D. P.; Behrens P. & Reifenrath J.
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Implant-directed magnetic drug targeting via multifunctional superparamagnetic silica core-shell nanoparticles, 117. Bunsentagung, 10.-12.05.2018, Hannover
Warwas, D. P.; Nolte, K.; Janßen, H. C.; Reifenrath, J.; Angrisani, N.; Kietzmann, M.; Meißner, J.; Taptimthong, P.; Wurz, M. C. & Behrens, P.
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In vitro and in vivo accumulation of magnetic nanoporous silica nanoparticles on implant materials with different magnetic properties. Journal of Nanobiotechnology, 16(1).
Janßen, Hilke Catherina; Warwas, Dawid Peter; Dahlhaus, David; Meißner, Jessica; Taptimthong, Piriya; Kietzmann, Manfred; Behrens, Peter; Reifenrath, Janin & Angrisani, Nina
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In vitro biocompatibility of magnetic nanoparticles used as potential drug carriers for implant‐directed magnetic drug targeting. J Vet Pharmacol Therap 41 (Suppl. 1), 111, 14th International Congress of the European Association for Veterinary Pharmacology and Toxicology, Wroclaw, Poland, 24.-27.6.2018
Dahlhaus D.; Meissner J.; Mielke-Kuschow S.; Warwas D. P.; Behrens P.; Reifenrath J.; Angrisani N.; Janssen H. C. & Kietzmann, M.
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Untersuchung von magnetischen Nanopartikeln hinsichtlich ihrer biologischen Verträglichkeit und der Nutzung als Wirkstoffträger, 2018, Dissertation, Stiftung Tierärztliche Hochschule Hannover
David Dahlhaus
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Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics. Journal of Nanobiotechnology, 18(1).
Janßen, Hilke Catherina; Angrisani, Nina; Kalies, Stefan; Hansmann, Florian; Kietzmann, Manfred; Warwas, Dawid Peter; Behrens, Peter & Reifenrath, Janin
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Implant-based direction of magnetic nanoporous silica nanoparticles – influence of macrophage depletion and infection. Nanomedicine: Nanotechnology, Biology and Medicine, 30, 102289.
Reifenrath, Janin; Janßen, Hilke Catherina; Warwas, Dawid Peter; Kietzmann, Manfred; Behrens, Peter; Willbold, Elmar; Fedchenko, Mykola & Angrisani, Nina
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Magnetische Nanopartikel als Wirkstoff-Carrier für die Therapie von Implantat-assoziierten Infektionen: Eine Untersuchung der Biokompatibilität, Verteilung und Akkumulation im Mausmodell, 2020, Dissertation, Stiftung Tierärztliche Hochschule Hannover
Hilke Catherina Janßen
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Adjusting the properties of magnetic core-shell nanoparticles by surface functionalization with PEG residues of different chain lengths, 6th Euro BioMAT 2021, 05.-06. Mai 2021, virtual, (Poster)
Herrmann T.; Behrens P.; Kietzmann M.; Noyun S.; Petrovic K.; Reifenrath J. & Schlerz A.
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In vitro biocompatibility evaluation of a magnetic nanoporous silica nanoparticle, 55th DGBMT Annual Conference on Biomedical Engineering (BMT 2021), 05.-07. Oktober 2021, Hannover (Vortrag)
Storjohann, R.; Oltmanns, H.; Herrmann, T.; Behrens, P.; Angrisani, N.; Reifenrath, J. & Meissner, J.
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PEG Functionalization of Magnetic Nanoporous Core-Shell Nanoparticles - Influence of the PEG Chain Length, 55th DGBMT Annual Conference on Biomedical Engineering (BMT 2021), 05.-07. Oktober 2021, Hannover (Poster)
Herrmann, T.; Schierz, A.; Noyun, S.; Petrović, K.; Reifenrath, J.; Kietzmann, M. & Behrens P.
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Biocompatibility of different PEGylated magnetic nanoporous silica nanoparticles in primary murine cells, VET- Pharm Symposium 1. – 2. September 2022, Hannover, Deutschland (Poster, Posterpreis)
Storjohann, R.; Gericke, B.; Oltmanns, H.; Herrmann, T.; Behrens, P.; Reifenrath, J. & Meißner, J.
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Das isoliert perfundierte Schafbein als Ex-vivo-Modell für pharmakologische Untersuchungen, 2022, Dissertation, Stiftung Tierärztliche Hochschule Hannover
Gerrit Hacker
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Effect of PEG functionalization on the saturation magnetization of magnetic nanoporous core-shell nanoparticles. Int J Mag Part Imag. 2022 8.
Herrmann T., Schierz A. K., Prediger M., Reifenrath J., Meißner J., Wurz M. C. & Behrens P.
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In-vitro-Untersuchungen zur Biokompatibilität und Immuntoxizität von magnetischen nanoporösen Silica-Nanopartikeln; 2022, Dissertation, Stiftung Tierärztliche Hochschule Hannover
Ronja Storjohann
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The isolated perfused ovine forelimb as an ex-vivo model for pharmacological research, Symposium des Virtuellen Zentrums für Ersatz- und Ergänzungsmethoden zum Tierversuch (VETZ), 24. - 25.02.2022, Hannover, Deutschland
Hacker, G.; Oltmanns, H.; Storjohann, R.; Herrmann, T.; Behrens, P.; Harting, H.; Reifenrath, J.; Angrisani, N. & Meißner, J.
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The isolated perfused ovine forelimb as an ex-vivo model for pharmacological research, VETPharm Symposium 1. – 2. September 2022, Hannover, Deutschland (Poster)
Hacker, G.; Oltmanns, H.; Herrmann, T.; Behrens, P.; Reifenrath, J.; Seeger, B. & Meißner, J.
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Influence of PEG Chain Length of Functionalized Magnetic Nanoparticles on the Cytocompatibility and Immune Competence of Primary Murine Macrophages and Dendritic Cells. International Journal of Molecular Sciences, 24(3), 2565.
Storjohann, Ronja; Gericke, Birthe; Reifenrath, Janin; Herrmann, Timo; Behrens, Peter; Oltmanns, Hilke & Meißner, Jessica
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Magnetische multifunktionale Nanopartikel für die Implantat-dirigierte Wirkstoffanlieferung, 2023, Dissertation, Leibniz Universität Hannover
Dawid Peter Warwas
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Preparation and PET/CT imaging of implant directed 68Ga-labeled magnetic nanoporous silica nanoparticles. Journal of Nanobiotechnology, 21(1).
Polyak, Andras; Harting, Heidi; Angrisani, Nina; Herrmann, Timo; Ehlert, Nina; Meißner, Jessica; Willmann, Michael; Al-Bazaz, Silav; Ross, Tobias L.; Bankstahl, Jens P. & Reifenrath, Janin
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Visualization of nanoporous silica nanoparticle distribution for implantdirected magnetic drug targeting by 68Ga-labeling and PET/CT EORS Congress 27. – 29.09.2023 Porto, Portugal (Vortrag)
Harting, H.; Polyak, A.; Angrisani, N.; Herrmann, T.; Ehlert, N.; Meißner, J.; Willmann, M.; Al-Bazaz, S.; Ross, T. L.; Bankstahl, J. P. & Reifenrath, J.
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Nanoporous silica nanoparticles as potential drug delivery tool in orthopedic implant associated infections, 12th World Biomaterials Congress, 26.- 31.05.2024, Deagu, South Korea (Poster)
Reifenrath, J.; Harting, H.; Polyak, A.; Herrmann, T.; Ehlert, N.; Meißner, J.; Willmann, M.; Al-Bazaz, S.; Ross, T. L.; Bankstahl, J. P. & Angrisani, N.
