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Small. 2019 Sep 4:e1904203. doi: 10.1002/smll.201904203. [Epub ahead of print]

Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain.

Author information

1
Faculty of Engineering, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
2
Bar-Ilan Institute of Nanotechnologies and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
3
Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, 3200003, Israel.
4
Department of Chemistry, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
5
Department of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
6
Department of Physics, University of California, San Diego, La Jolla, CA, 92093, USA.
7
Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa, 3200003, Israel.

Abstract

Nerve growth factor (NGF) plays a vital role in reducing the loss of cholinergic neurons in Alzheimer's disease (AD). However, its delivery to the brain remains a challenge. Herein, NGF is loaded into degradable oxidized porous silicon (PSiO2 ) carriers, which are designed to carry and continuously release the protein over a 1 month period. The released NGF exhibits a substantial neuroprotective effect in differentiated rat pheochromocytoma PC12 cells against amyloid-beta (Aβ)-induced cytotoxicity, which is associated with Alzheimer's disease. Next, two potential localized administration routes of the porous carriers into murine brain are investigated: implantation of PSiO2 chips above the dura mater, and biolistic bombardment of PSiO2 microparticles through an opening in the skull using a pneumatic gene gun. The PSiO2 -implanted mice are monitored for a period of 8 weeks and no inflammation or adverse effects are observed. Subsequently, a successful biolistic delivery of these highly porous microparticles into a live-mouse brain is demonstrated for the first time. The bombarded microparticles are observed to penetrate the brain and reach a depth of 150 µm. These results pave the way for using degradable PSiO2 carriers as potential localized delivery systems for NGF to the brain.

KEYWORDS:

Alzheimer's disease; biolistics; brain; delivery; nerve growth factor; porous silicon

PMID:
31482695
DOI:
10.1002/smll.201904203

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