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The use of magnetite nanoparticles for implant-assisted magnetic drug targeting in thrombolytic therapy.

Kempe, Henrik LU and Kempe, Maria LU (2010) In Biomaterials 31. p.9499-9510
Abstract
Implant-assisted targeting of magnetic particles under the influence of an external magnetic field has previously been verified through mathematical modeling, in vitro studies, and in vivo studies on rat carotid arteries as a feasible method for localized drug delivery. The present study focuses on the development of nanoparticles for the treatment of in-stent thrombosis. Magnetic nanoparticles in the size-range 10-30 nm were synthesized in a one-pot procedure by precipitation of ferrous hydroxide followed by oxidation to magnetite. The nanoparticles were silanized with tetraethyl orthosilicate in the presence of triethylene glycol and/or polyethylene glycol. The surface coated magnetite nanoparticles were activated with either... (More)
Implant-assisted targeting of magnetic particles under the influence of an external magnetic field has previously been verified through mathematical modeling, in vitro studies, and in vivo studies on rat carotid arteries as a feasible method for localized drug delivery. The present study focuses on the development of nanoparticles for the treatment of in-stent thrombosis. Magnetic nanoparticles in the size-range 10-30 nm were synthesized in a one-pot procedure by precipitation of ferrous hydroxide followed by oxidation to magnetite. The nanoparticles were silanized with tetraethyl orthosilicate in the presence of triethylene glycol and/or polyethylene glycol. The surface coated magnetite nanoparticles were activated with either N-hydroxysulfosuccinimide or tresyl chloride for covalent immobilization of tissue plasminogen activator (tPA). Hysteresis loops showed saturation magnetizations of 55.8, 44.1, and 43.0 emu/g for the naked nanoparticles, the surface coated nanoparticles, and the tPA-nanoparticle conjugates, respectively. The hemolytic activity of the nanoparticles in blood was negligible. An initial in vivo biocompatibility test in pig, carried out by intravascular injection of the nanoparticles in a stented brachial artery, showed no short-term adverse effects. In vitro evaluation in a flow-through model proved that the nanoparticles were captured efficiently to the surface of a ferromagnetic coiled wire at the fluid velocities typical for human arteries. A preliminary test of the tPA-nanoparticle conjugates in a pig model suggested that the conjugates may be used for treatment of in-stent thrombosis in coronary arteries. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Biomaterials
volume
31
pages
9499 - 9510
publisher
Elsevier
external identifiers
  • wos:000285120800014
  • pmid:20732712
  • scopus:78149414882
ISSN
1878-5905
DOI
10.1016/j.biomaterials.2010.07.107
language
English
LU publication?
yes
id
f091797a-f48c-4c46-8875-7b9fe577454b (old id 1665082)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20732712?dopt=Abstract
date added to LUP
2010-09-14 09:52:41
date last changed
2018-07-15 03:14:59
@article{f091797a-f48c-4c46-8875-7b9fe577454b,
  abstract     = {Implant-assisted targeting of magnetic particles under the influence of an external magnetic field has previously been verified through mathematical modeling, in vitro studies, and in vivo studies on rat carotid arteries as a feasible method for localized drug delivery. The present study focuses on the development of nanoparticles for the treatment of in-stent thrombosis. Magnetic nanoparticles in the size-range 10-30 nm were synthesized in a one-pot procedure by precipitation of ferrous hydroxide followed by oxidation to magnetite. The nanoparticles were silanized with tetraethyl orthosilicate in the presence of triethylene glycol and/or polyethylene glycol. The surface coated magnetite nanoparticles were activated with either N-hydroxysulfosuccinimide or tresyl chloride for covalent immobilization of tissue plasminogen activator (tPA). Hysteresis loops showed saturation magnetizations of 55.8, 44.1, and 43.0 emu/g for the naked nanoparticles, the surface coated nanoparticles, and the tPA-nanoparticle conjugates, respectively. The hemolytic activity of the nanoparticles in blood was negligible. An initial in vivo biocompatibility test in pig, carried out by intravascular injection of the nanoparticles in a stented brachial artery, showed no short-term adverse effects. In vitro evaluation in a flow-through model proved that the nanoparticles were captured efficiently to the surface of a ferromagnetic coiled wire at the fluid velocities typical for human arteries. A preliminary test of the tPA-nanoparticle conjugates in a pig model suggested that the conjugates may be used for treatment of in-stent thrombosis in coronary arteries.},
  author       = {Kempe, Henrik and Kempe, Maria},
  issn         = {1878-5905},
  language     = {eng},
  pages        = {9499--9510},
  publisher    = {Elsevier},
  series       = {Biomaterials},
  title        = {The use of magnetite nanoparticles for implant-assisted magnetic drug targeting in thrombolytic therapy.},
  url          = {http://dx.doi.org/10.1016/j.biomaterials.2010.07.107},
  volume       = {31},
  year         = {2010},
}