TY - JOUR
T1 - Prolonged controlled delivery of nerve growth factor using porous silicon nanostructures
AU - Zilony, Neta
AU - Rosenberg, Michal
AU - Holtzman, Liran
AU - Schori, Hadas
AU - Shefi, Orit
AU - Segal, Ester
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2017/7/10
Y1 - 2017/7/10
N2 - 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 > 26 days. 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.
AB - 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 > 26 days. 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.
KW - Controlled release
KW - Differentiation
KW - Dorsal root ganglia
KW - Nerve growth factor
KW - PC12
KW - Porous silicon
UR - http://www.scopus.com/inward/record.url?scp=85008233916&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2016.12.008
DO - 10.1016/j.jconrel.2016.12.008
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C2 - 27988302
AN - SCOPUS:85008233916
SN - 0168-3659
VL - 257
SP - 51
EP - 59
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -