Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

Abstract

BackgroundIn orthopaedic surgery, accumulation of agents such as anti-infectives in the bone as target tissue is difficult. The use of magnetic nanoparticles (MNPs) as carriers principally enables their accumulation via an externally applied magnetic field. Magnetizable implants are principally able to increase the strength of an externally applied magnetic field to reach also deep-seated parts in the body. Therefore, the integration of bone-addressed therapeutics in MNPs and their accumulation at a magnetic orthopaedic implant could improve the treatment of implant related infections. In this study a martensitic steel platelet as implant placeholder was used to examine its accumulation and retention capacity of MNPs in an in vitro experimental set up considering different experimental frame conditions as magnet quantity and distance to each other, implant thickness and flow velocity.ResultsThe magnetic field strength increased to approximately 112% when a martensitic stainless steel platelet was located between the magnet poles. Therewith a significantly higher amount of magnetic nanoparticles could be accumulated in the area of the platelet compared to the sole magnetic field. During flushing of the tube system mimicking the in vivo blood flow, the magnetized platelet was able to retain a higher amount of MNPs without an external magnetic field compared to the set up with no mounted platelet during flushing of the system. Generally, a higher flow velocity led to lower amounts of accumulated MNPs. A higher quantity of magnets and a lower distance between magnets led to a higher magnetic field strength. Albeit not significantly the magnetic field strength tended to increase with thicker platelets.ConclusionA martensitic steel platelet significantly improved the attachment of magnetic nanoparticles in an in vitro flow system and therewith indicates the potential of magnetic implant materials in orthopaedic surgery. The use of a remanent magnetic implant material could improve the efficiency of capturing MNPs especially when the external magnetic field is turned off thus facilitating and prolonging the effect. In this way higher drug levels in the target area might be attained resulting in lower inconveniences for the patient.

Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics

“…Secondly, it was hypothesized that MNPSNPs are available in the implantation area. And thirdly, based on the results of previous in vitro and in vivo studies [26,53,54], an externally magnetized ferromagnetic implant material was supposed to be able to accumulate these nanoparticles at the implant surface in higher concentrations than the control. This would mean a safe use of MNPSNPs as future drug carrier system for implantassociated infection treatment.…”

“…As a treatment strategy in case of occurring implantassociated infection in orthopedics, implant-directed magnetic drug targeting (ID-MDT) represents a possible approach to reduce systemic antibiotic doses, period and therefore side effects and probably the need of revision surgeries. Locally high and sufficient levels of antibiotics might be achieved by loading magnetic nanoparticles with these antibiotics and target them by magnetic force towards the implant, followed by triggered drug-release [24][25][26].…”

Nanoparticulate Platforms for Targeting Bone Infections: Meeting a Major Therapeutic Challenge

“…In particular, magnetite nanoparticles coated with either a silica or a calcium phosphate layer have been studied due to their ability to concentrate around metal implants and therefore be able to release antibiotics locally [51,64]. Although this might be a promising strategy, these systems are still in an early stage of development and so far no antibiotics have been incorporated into these systems.…”

“…The CS/Ag/HA coatings are active against both S. epidermidis and E. coli and exhibited good biocompatibility in osteoblasts [62] Metal plates coated with titanium oxide nanoparticles After 50 min of UV-photoactivation Ti nanoparticles showed a complete bactericidal effect against E. coli, Pseudomonas aeruginosa, S. aureus, Enterococcus hirae and Bacteroides fragilis [63] Magnetic Magnetite (Fe 3 O 4 ) nanoparticles enclosed by a nanoporous silica layer Possible future incorporation of drugs into the silica layer [64] Magnetite nanoparticles coated with calcium phosphate…”

“…These may be included in the composition of medical devices, either by incorporation in PMMA and HA bone cements and hydrogels or used for coating of metal implants (Table 2). In addition, a new research trend has been focusing on the targeted antibiotic delivery to the surrounding areas of metallic implants by using magnetic nanoparticles composed of magnetite [50,51].…”