Premium
Neuroprotective Effect of Nerve Growth Factor Loaded in Porous Silicon Nanostructures in an Alzheimer's Disease Model and Potential Delivery to the Brain
Author(s) -
ZilonyHanin Neta,
Rosenberg Michal,
Richman Michal,
Yehuda Ronen,
Schori Hadas,
Motiei Menachem,
Rahimipour Shai,
Groisman Alexander,
Segal Ester,
Shefi Orit
Publication year - 2019
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201904203
Subject(s) - nerve growth factor , neuroprotection , porous silicon , cytotoxicity , drug delivery , cholinergic neuron , materials science , chemistry , biophysics , pharmacology , microbiology and biotechnology , neuroscience , medicine , central nervous system , cancer research , nanotechnology , endocrinology , biology , silicon , biochemistry , in vitro , receptor , metallurgy
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 (PSiO 2 ) 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 PSiO 2 chips above the dura mater, and biolistic bombardment of PSiO 2 microparticles through an opening in the skull using a pneumatic gene gun. The PSiO 2 ‐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 PSiO 2 carriers as potential localized delivery systems for NGF to the brain.