New Therapeutic Approaches to Administer Nerve Growth Factor into the Brain Using Porous Silicon Nanostructures

Nerve growth factor (NGF) is essential for neuronal differentiation and has a crucial role in the development and maintenance of neurons in the peripheral and central nervous systems (PNS and CNS). NGF deficiency leads to brain pathologies and therefore its exogenous delivery presents high pharmacological potential for treating neurodegenerative diseases, including Alzheimer’s and Parkinson’s. However, NGF delivery to the CNS represents a significant challenge due to its inability to cross the blood brain barrier. Therefore, there is an immense need to develop new administration routes for long-term delivery systems that will allow for spatiotemporal release of NGF. Nanostructured porous silicon (PSi) is characterized by several appealing properties, such as its high surface area, large porous volume, biocompatibility, and tunable degradability in physiological environment, predestining it for a promising drug delivery platform. Herein, we present new therapeutic approaches to administer NGF to the brain by implantation of PSi-based implants of NGF reservoirs or by biolistic delivery of NGF-loaded PSi microparticles. Fluorescently-labeled PSi carries are implanted in mice brains and the implanted mice are observed to live and function normally throughout the 8-week study. Fluorescence-intensity distribution in the dissected brains, combined with Inductively coupled plasma atomic emission spectroscopy (ICP-AES), are employed for monitoring Si degradation process of the carriers in the brain tissue. Moreover, the therapeutic efficacy of the platform is successfully verified using an in-vitro Alzheimer’s disease model. Another approach to administer the NGF-PSi carriers with a high spatial resolution is by biolistic techniques. NGF-loaded PSi microparticles are bombarded into the brain using a novel gene gun set-up. Following administration of the carriers, spatial distribution of the PSi particles, as well as histology and ICP-AES analyses, are performed to evaluate bombardment efficiency. We show that both strategies hold immense potential as promising approaches to overcome the current limitations of NGF-based therapies.

*The authors contributed equally to this work.