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

J Control Release. 2019 Jan 10;293:63-72. doi: 10.1016/j.jconrel.2018.11.017. Epub 2018 Nov 17.

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 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.

Keywords: BBB; Brain; Drug delivery; MEK; NGF; Nanoparticles; Theranostic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / administration & dosage*
  • Animals
  • Apolipoproteins E / administration & dosage
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Butadienes / administration & dosage*
  • Drug Carriers / administration & dosage*
  • Drug Therapy, Combination
  • Ferric Compounds / administration & dosage*
  • Infarction, Middle Cerebral Artery / diagnostic imaging
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / pathology
  • Male
  • Nanoparticles / administration & dosage*
  • Nerve Growth Factor / administration & dosage*
  • Nitriles / administration & dosage*
  • PC12 Cells
  • Protein Kinase Inhibitors / administration & dosage*
  • Rats
  • Rats, Wistar
  • Theranostic Nanomedicine

Substances

  • Albumins
  • Apolipoproteins E
  • Butadienes
  • Drug Carriers
  • Ferric Compounds
  • Nitriles
  • Protein Kinase Inhibitors
  • U 0126
  • ferric oxide
  • Nerve Growth Factor