title: Prolonged controlled delivery of nerve growth factor using porous silicon nanostructures.
abstract: 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 the difficulty to locally deliver relevant doses in a safe and non-invasive manner. In this work, we employ degradable nanostructured porous silicon (PSi) films as carriers for NGF, allowing its continuous and prolonged release, while retaining its bioactivity. The PSi carriers exhibit high loading efficacy (up to 90%) of NGF and a continuous release, with no burst, over a period of>26days. The released NGF bioactivity is compared to that of free NGF in both PC12 cells and dissociated dorsal root ganglion (DRG) neurons. We show that the NGF has retained its bioactivity and induces neurite outgrowth and profound differentiation (of >50% for PC12 cells) throughout the period of release within a single administration. Thus, this proof-of-concept study demonstrates the immense therapeutic potential of these tunable carriers as long-term implants of NGF reservoirs and paves the way for new localized treatment strategies of neurodegenerative diseases.
authors.affiliation: Faculty of Engineering, Bar-Ilan University, Ramat-Gan 52900, Israel; Bar-Ilan Institute of Nanotechnologies and Advanced Materials, Ramat-Gan 52900, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Zilony
authors.affiliation: Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Rosenberg
authors.affiliation: Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Liran
authors.initials: L
authors.lastname: Holtzman
authors.affiliation: Faculty of Engineering, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Schori
authors.affiliation: Faculty of Engineering, Bar-Ilan University, Ramat-Gan 52900, Israel; Bar-Ilan Institute of Nanotechnologies and Advanced Materials, Ramat-Gan 52900, Israel. Electronic address: orit.shefi@biu.ac.il.
authors.forename: Orit
authors.initials: O
authors.lastname: Shefi
authors.affiliation: Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel; Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa 32000, Israel. Electronic address: esegal@technion.ac.il.
authors.forename: Ester
authors.initials: E
authors.lastname: Segal
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000737:chemistry*; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016716:PC12 Cells; D016062:Porosity; D051381:Rats; D012825:Silicon / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D009414:Nerve Growth Factors; D012825:Silicon
keywords: Controlled release; Differentiation; Dorsal root ganglia; Nerve growth factor; PC12; Porous silicon