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

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)

Intrauterine therapy of fetal tachyarrhythmias: Intraperitoneal administration of antiarrhythmic drugs to the fetus in fetal tachyarrhythmias with severe hydrops fetalis

Peer Reviewe

Three-dimensional sonographic evaluation of the fetal lumbar spinal canal

In a prospective cross-sectional ultrasound study the size of the fetal lumbar spinal canal was evaluated to determine reference values for the lumbar part of the vertebral canal. One hundred and sixty-seven pregnant women undergoing routine obstetric ultrasound were studied between 16 and 41 weeks of gestation. Exclusion criteria consisted of structural fetal anomalies or growth restriction. Area and volume of the vertebral canal at L1, L3 and L5 were calculated by three-dimensional (3D) ultrasound. Length of the lumbar spine was also determined. The size of the spinal canal and spinal length correlated well with gestational age. No gestational-age-dependent differences in area and volume measurements between upper and lower lumbar spine were found. The results provide an in vivo assessment of the spinal canal by 3D ultrasound over the entire gestation period