Details
| Original language | English |
|---|---|
| Article number | 14 |
| Number of pages | 18 |
| Journal | Journal of nanobiotechnology |
| Volume | 18 |
| Issue number | 1 |
| Publication status | Published - 15 Jan 2020 |
Abstract
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.
Keywords
- Drug targeting, Ferritic steel, In vivo, Magnetic nanoporous silica nanoparticles, Magnetizable implant, Mouse model, Organ accumulation, PEG, Silicon Dioxide/chemistry, Hindlimb, Drug Carriers/administration & dosage, Silanes/chemistry, Magnetite Nanoparticles/chemistry, Prostheses and Implants, Fluorescent Dyes/chemistry, Rhodamines/chemistry, Tissue Distribution, Animals, Orthopedics, Polyethylene Glycols/chemistry, Female, Mice, Inbred BALB C, Porosity, Ferric Compounds/chemistry
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Applied Microbiology and Biotechnology
- Chemical Engineering(all)
- Bioengineering
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Medicine
- Engineering(all)
- Biomedical Engineering
- Medicine(all)
- Medicine (miscellaneous)
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
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In: Journal of nanobiotechnology, Vol. 18, No. 1, 14, 15.01.2020.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics
AU - Janßen, Hilke Catherina
AU - Angrisani, Nina
AU - Kalies, Stefan
AU - Hansmann, Florian
AU - Kietzmann, Manfred
AU - Warwas, Dawid Peter
AU - Behrens, Peter
AU - Reifenrath, Janin
N1 - Funding information: This work was supported by the DFG project “Implant-Directed Magnetic Drug Targeting: Antibiotic therapy of peri-implant infections”, project number: 280642759.
PY - 2020/1/15
Y1 - 2020/1/15
N2 - 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.
AB - 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.
KW - Drug targeting
KW - Ferritic steel
KW - In vivo
KW - Magnetic nanoporous silica nanoparticles
KW - Magnetizable implant
KW - Mouse model
KW - Organ accumulation
KW - PEG
KW - Silicon Dioxide/chemistry
KW - Hindlimb
KW - Drug Carriers/administration & dosage
KW - Silanes/chemistry
KW - Magnetite Nanoparticles/chemistry
KW - Prostheses and Implants
KW - Fluorescent Dyes/chemistry
KW - Rhodamines/chemistry
KW - Tissue Distribution
KW - Animals
KW - Orthopedics
KW - Polyethylene Glycols/chemistry
KW - Female
KW - Mice, Inbred BALB C
KW - Porosity
KW - Ferric Compounds/chemistry
UR - http://www.scopus.com/inward/record.url?scp=85077941758&partnerID=8YFLogxK
U2 - 10.1186/s12951-020-0578-8
DO - 10.1186/s12951-020-0578-8
M3 - Article
C2 - 31941495
AN - SCOPUS:85077941758
VL - 18
JO - Journal of nanobiotechnology
JF - Journal of nanobiotechnology
SN - 1477-3155
IS - 1
M1 - 14
ER -