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

Neta Zilony-Hanin; Michal Rosenberg; Michal Richman; Ronen Yehuda; Hadas Schori; Menachem Motiei; Shai Rahimipour; Alexander Groisman; Ester Segal; Orit Shefi

doi:10.1002/smll.201904203

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

Small. 2019 Nov;15(45):e1904203. doi: 10.1002/smll.201904203. Epub 2019 Sep 4.

Authors

Neta Zilony-Hanin^{1

2}, Michal Rosenberg³, Michal Richman⁴, Ronen Yehuda⁵, Hadas Schori¹, Menachem Motiei^{1

2}, Shai Rahimipour⁴, Alexander Groisman⁶, Ester Segal^{3

7}, Orit Shefi^{1

2}

Affiliations

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.

PMID: 31482695
DOI: 10.1002/smll.201904203

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / drug therapy*
Alzheimer Disease / metabolism*
Animals
Brain / metabolism*
Cell Survival / drug effects
Mice
Microscopy, Confocal
Microscopy, Fluorescence
Nanostructures / chemistry*
Nanostructures / therapeutic use
Nerve Growth Factor / chemistry*
Nerve Growth Factor / pharmacokinetics
Nerve Growth Factor / therapeutic use*
PC12 Cells
Porosity
Rats
Silicon / chemistry*
X-Ray Microtomography

Substances

Nerve Growth Factor
Silicon