Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics
Creators: name: Janßen, Hilke Catherina
name: Angrisani, Nina
name: Kalies, Stefan
name: Hansmann, Florian
name: Kietzmann, Manfred
name: Warwas, Dawid Peter
name: Behrens, Peter
name: Reifenrath, Janin
Publisher: name: London : BioMed Central Ltd.
Year: 2020
Subjects: subject: Drug targeting
subject: Ferritic steel
subject: In vivo
subject: Magnetic nanoporous silica nanoparticles
subject: Magnetizable implant
subject: Mouse model
subject: Organ accumulation
subject: PEG
subject: Aluminum alloys
subject: Antibiotics
subject: Biocompatibility
subject: Biological organs
subject: Controlled drug delivery
subject: Drug dosage
subject: Ferrite
subject: Ferritic stainless steel
subject: Histology
subject: Magnetic fields
subject: Mammals
subject: Nanomagnetics
subject: Nanoparticles
subject: Orthopedics
subject: Polyethylene glycols
subject: Polymeric implants
subject: Silica
subject: Silica nanoparticles
subject: Ternary alloys
subject: Titanium alloys
subject: Vanadium alloys
subject: Drug-targeting
subject: In-vivo
subject: Magnetic nanoporous silicas
subject: Mouse models
subject: Targeted drug delivery
subject: drug carrier
subject: isothiocyanic acid
subject: macrogol
subject: magnetic nanoporous silica nanoparticle
subject: rhodamine B
subject: silane
subject: steel
subject: unclassified drug
subject: animal experiment
subject: animal tissue
subject: Article
subject: bioaccumulation
subject: biocompatibility
subject: controlled study
subject: drug transport
subject: female
subject: in vivo study
subject: magnetic field
subject: mouse
subject: nonhuman
subject: orthopedics
subject: tissue distribution
subject: Dewey Decimal Classification::500 | Naturwissenschaften::540 | Chemie
subject: Dewey Decimal Classification::600 | Technik::610 | Medizin, Gesundheit

description: Background: In orthopedics, the treatment of implant-associated infections represents a high challenge. Especially, potent antibacterial effects at implant surfaces can only be achieved by the use of high doses of antibiotics, and still often fail. Drug-loaded magnetic nanoparticles are very promising for local selective therapy, enabling lower systemic antibiotic doses and reducing adverse side effects. The idea of the following study was the local accumulation of such nanoparticles by an externally applied magnetic field combined with a magnetizable implant. The examination of the biodistribution of the nanoparticles, their effective accumulation at the implant and possible adverse side effects were the focus. In a BALB/c mouse model (n = 50) ferritic steel 1.4521 and Ti90Al6V4 (control) implants were inserted subcutaneously at the hindlimbs. Afterwards, magnetic nanoporous silica nanoparticles (MNPSNPs), modified with rhodamine B isothiocyanate and polyethylene glycol-silane (PEG), were administered intravenously. Directly/1/7/21/42 day(s) after subsequent application of a magnetic field gradient produced by an electromagnet, the nanoparticle biodistribution was evaluated by smear samples, histology and multiphoton microscopy of organs. Additionally, a pathohistological examination was performed. Accumulation on and around implants was evaluated by droplet samples and histology. Results: Clinical and histological examinations showed no MNPSNP-associated changes in mice at all investigated time points. Although PEGylated, MNPSNPs were mainly trapped in lung, liver, and spleen. Over time, they showed two distributional patterns: early significant drops in blood, lung, and kidney and slow decreases in liver and spleen. The accumulation of MNPSNPs on the magnetizable implant and in its area was very low with no significant differences towards the control. Conclusion: Despite massive nanoparticle capture by the mononuclear phagocyte system, no significant pathomorphological alterations were found in affected organs. This shows good biocompatibility of MNPSNPs after intravenous administration. The organ uptake led to insufficient availability of MNPSNPs in the implant region. For that reason, among others, the nanoparticles did not achieve targeted accumulation in the desired way, manifesting future research need. However, with different conditions and dimensions in humans and further modifications of the nanoparticles, this principle should enable reaching magnetizable implant surfaces at any time in any body region for a therapeutic reason. © 2020 The Author(s).