The field of nanoparticle related research for the diagnosis and therapy of diseases evolves rapidly. Magnetic nanoparticles in combination with magnetizable implant materials for the treatment of implant related infections present a possible implementation in orthopedics. Magnetic nanoporous silica nanoparticles (MNPSNPs) were developed and equipped with fluorescent dyes. In vitro/in vivo biocompatibility and in vivo biodistribution were examined to appraise their potential applicability. Cell culture tests with NIH-3T3 and HepG2 cell lines indicated a good in vitro biocompatibility. Ferritic and titanium alloy (control) plates were implanted subcutaneously at the hind legs of Balb/c mice. Immediately after i.v. or s.c. injection of MNPSNPs, the caudal half of the mice was placed between the poles of an electro magnet. Exposure to the electromagnetic field of approx. 1.7 T was maintained for 10 minutes. 10 animals each were euthanized at days 0, 1, 7, 21 or 42, respectively. Quantity of MNPSNPs in liver, spleen, kidney, lung and skin/muscle samples was assessed by fluorescent microscopic methods. MNPSNP existence on the implant surface was also appraised after several steps of detachment. MNPSNPs showed a time-dependent accumulation in the organs after i.v. injection with initial accumulation in the lungs followed by redistribution to liver and spleen. After s.c. injection no systemic distribution but local appearance of MNPSNPs could be found. First histological evaluation showed no pathological changes after i.v. injection. With good in vivo biocompatibility, future focus will be laid on increasing circle life time of MNPSNPs and evaluation in an infection model.

After the implantation of endoprotheses or osteosynthesis devices, implant-related infections are one of the major challenges. The surface of implants offers optimal conditions for the formation of a biofilm. Effective carrier systems for the delivery of adequate therapeutics would reduce the concentrations needed for successful treatment and improve cure rates. In cancer diagnosis and therapy, magnetic nanoparticles are concentrated in the target area by an external magnetic field. For orthopaedic applications, in vitro examinations showed that the addition of a magnetic implant in combination with an external magnetic field could increase the amount of MNPSNPs that accumulated in direct vicinity to the implant. The present examinations implemented an electromagnet to increase magnetic field strength and should show if the in vitro set up can be transferred to an in vivo mouse model. Additionally, the loading capacity of the MNPSNPs with enrofloxacin and its release kinetics were determined.

Fluorescein-isothiocyanate (FITC) was covalently attached to MNPSNPs. For the in vitro set up, a peristaltic pump was used to establish a closed circuit which contained the MNPSNP dispersion and a magnetic platelet. After 5 minutes fluid samples were taken from the area around the magnetic platelet and analysed using a microplate reader. For the in vivo set up, a BALB/c mouse was implanted subcutaneously with the metallic platelet at the hind leg. The MNPSNP dispersion was injected into the tale vein and the hind leg of the mouse was placed immediately in a magnetic field of 1.9 T. After one week the implant was retrieved and examined by confocal laser scanning microscopy (CLSM). Liver, spleen and kidneys of the mouse were examined by magnetic resonance imaging (MRI). The loading capacity of the MNPs with enrofloxacin was examined by quantification of the enrofloxacin content in the incubation and washing solution after incubation. The release kinetics weres tested in PBS using UV/Vis-spectrometry.

The solution in the remaining tube contained no detectable MNPs while the concentration in the vicinity of the platelet was 150 µg/ml. The mouse showed no clinical adverse effects. The CLSM examination revealed a considerable accumulation of the MNPs at the implant surface. MRI could show neither accumulated MNPs nor changes of organ structure. The loading capacity of the MNPs for enrofloxacin was approximately 95 µg/mg. A burst release of nearly a third of the loaded antibiotic occurred within the first 6 hours followed by a further steady release.