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Stimulating brain recovery after stroke using theranostic albumin nanocarriers loaded with nerve growth factor in combination therapy

Feczkó, Tivadar; Piiper, Albrecht; Ansar, Saema LU ; Blixt, Frank W. LU ; Ashtikar, Mukul; Schiffmann, Susanne; Ulshöfer, Thomas; Parnham, Michael J.; Harel, Yifat and Israel, Liron Limor, et al. (2019) In Journal of Controlled Release 293. p.63-72
Abstract

For many years, delivering drug molecules across the blood brain barrier has been a major challenge. The neuropeptide nerve growth factor is involved in the regulation of growth and differentiation of cholinergic neurons and holds great potential in the treatment of stroke. However, as with many other compounds, the biomolecule is not able to enter the central nervous system. In the present study, nerve growth factor and ultra-small particles of iron oxide were co-encapsulated into a chemically crosslinked albumin nanocarrier matrix which was modified on the surface with apolipoprotein E. These biodegradable nanoparticles with a size of 212 ± 1 nm exhibited monodisperse size distribution and low toxicity. They delivered NGF through an... (More)

For many years, delivering drug molecules across the blood brain barrier has been a major challenge. The neuropeptide nerve growth factor is involved in the regulation of growth and differentiation of cholinergic neurons and holds great potential in the treatment of stroke. However, as with many other compounds, the biomolecule is not able to enter the central nervous system. In the present study, nerve growth factor and ultra-small particles of iron oxide were co-encapsulated into a chemically crosslinked albumin nanocarrier matrix which was modified on the surface with apolipoprotein E. These biodegradable nanoparticles with a size of 212 ± 1 nm exhibited monodisperse size distribution and low toxicity. They delivered NGF through an artificial blood brain barrier and were able to induce neurite outgrowth in PC12 cells in vitro. In an animal model of stroke, the infarct size was significantly reduced compared to the vehicle control. The combination therapy of NGF and the small-molecular MEK inhibitor U0126 showed a slight but not significant difference compared to U0126 alone. However, further in vivo evidence suggests that successful delivery of the neuropeptide is possible as well as the synergism between those two treatments.

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type
Contribution to journal
publication status
published
subject
keywords
BBB, Brain, Drug delivery, MEK, Nanoparticles, NGF, Theranostic
in
Journal of Controlled Release
volume
293
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:85057017478
ISSN
0168-3659
DOI
10.1016/j.jconrel.2018.11.017
language
English
LU publication?
yes
id
c495b0fd-f2a1-4c24-a9e9-dbc84cdd69b8
date added to LUP
2018-12-03 09:32:51
date last changed
2019-02-20 11:38:32
@article{c495b0fd-f2a1-4c24-a9e9-dbc84cdd69b8,
  abstract     = {<p>For many years, delivering drug molecules across the blood brain barrier has been a major challenge. The neuropeptide nerve growth factor is involved in the regulation of growth and differentiation of cholinergic neurons and holds great potential in the treatment of stroke. However, as with many other compounds, the biomolecule is not able to enter the central nervous system. In the present study, nerve growth factor and ultra-small particles of iron oxide were co-encapsulated into a chemically crosslinked albumin nanocarrier matrix which was modified on the surface with apolipoprotein E. These biodegradable nanoparticles with a size of 212 ± 1 nm exhibited monodisperse size distribution and low toxicity. They delivered NGF through an artificial blood brain barrier and were able to induce neurite outgrowth in PC12 cells in vitro. In an animal model of stroke, the infarct size was significantly reduced compared to the vehicle control. The combination therapy of NGF and the small-molecular MEK inhibitor U0126 showed a slight but not significant difference compared to U0126 alone. However, further in vivo evidence suggests that successful delivery of the neuropeptide is possible as well as the synergism between those two treatments.</p>},
  author       = {Feczkó, Tivadar and Piiper, Albrecht and Ansar, Saema and Blixt, Frank W. and Ashtikar, Mukul and Schiffmann, Susanne and Ulshöfer, Thomas and Parnham, Michael J. and Harel, Yifat and Israel, Liron Limor and Lellouche, Jean Paul and Wacker, Matthias G.},
  issn         = {0168-3659},
  keyword      = {BBB,Brain,Drug delivery,MEK,Nanoparticles,NGF,Theranostic},
  language     = {eng},
  pages        = {63--72},
  publisher    = {Elsevier},
  series       = {Journal of Controlled Release},
  title        = {Stimulating brain recovery after stroke using theranostic albumin nanocarriers loaded with nerve growth factor in combination therapy},
  url          = {http://dx.doi.org/10.1016/j.jconrel.2018.11.017},
  volume       = {293},
  year         = {2019},
}