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

Background: Although nerve growth factor (NGF) is beneficial for the treatment of numerous neurological and non-neurological diseases, its therapeutic administration represents a significant challenge due to its inability to cross the blood brain barrier. Nanostructured porous silicon (PSi) is characterized by several appealing properties, such as 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. Moreover, the therapeutic efficacy of the platform is successfully verified using an in-vitro Alzheimer’s disease model. Methods: Fluorescently-labeled PSi chips are implanted in mice brains and monitored for 8 weeks. Fluorescence-intensity distribution in the dissected brains, combined with ICP-AES, are employed for monitoring Si degradation process in the brain tissue. For the second approach, fluorescently-labeled PSi microparticles are biolistically bombarded into the brain using a novel gene gun set-up. Results: The implanted mice are observed to live and function normally throughout the 8-week study. Analysis of fluorescent images of the dissected brains demonstrates a deep homogeneous distribution of the degraded Si along a vertical plane of the brain tissue. The bombarded particles are delivered to a maximal penetration depth of 150 µm. Furthermore, NGF released from the carriers exhibits neuroprotective effect against Aβ-induced cytotoxicity. Conclusion: We show that both strategies hold immense potential as promising approaches to overcome the current limitations of NGF-based therapies.