Prolonged Controlled Delivery of Nerve Growth Factor using Porous Silicon Nanostructures as a Potential Alzheimer’s Disease Treatment

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. Moreover, NGF effectiveness in therapeutics is limited by its short biological half-life due to rapid enzymatic degradation in-vivo. 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. Our work aims to develop PSi-based carriers as long-term implants of NGF reservoirs for the prolonged controlled delivery of NGF in a localized and safe manner. The porous carriers, fabricated by electrochemical etching, demonstrate high loading efficacy (of up to 90%) of NGF and a continuous and sustained release over a period of ~1 month. The therapeutic efficacy of the NGF-PSi carriers is studied in vitro by examining their effect on neuronal differentiation of PC12 cells and dissociated dorsal root ganglion (DRG) neurons. We show that the entrapment of the protein within the nanostructured PSi carriers increases its stability and preserves its bioactivity for stimulating neurite outgrowth over a 1-month period. Furthermore, the efficacy of the platform is studied in vivo by its implantation in mice brains. Following administration of the NGF-PSi carriers to the brain tissue, Si degradation process and spatial distribution of the growth factor are examined, along with the potential therapeutic implications.

*Michal Rosenberg and Neta Zilony contributed equally to this work.