Drug Delivery Systems

Porous Si has emerged over the past several years as a promising nanomaterial for biomedical applications in general and drug delivery in particular. 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.
We develop PSi-based carriers as long-term implants of nerve growth factor (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.

Characterization of PSiO2 films and their loading and release behavior. (a–b) Top-view and cross-section HRSEM images of a typical PSiO2 film etched at a current density of 250 mA/cm2 for 67 s. (c) NGF release and Si degradation profiles of thin and thick PSiO2 carriers. (d) Average values of NGF loading (gray) for the different PSiO2 carriers and the corresponding accumulative values of NGF release (white). These results demonstrate that the PSiO2 carriers exhibit high loading efficacy (of up to 90%) of NGF and a continuous and sustained release over a period of ~1 month.

Neurite outgrowth of DRG neuronal cell culture. Representative confocal microscopy images of immunostained DRG neuronal cell culture (2 days after seeding): (a) untreated cells (no NGF); (b) cells supplemented with free NGF at a concentration of 50 ng/mL; (c) cells cultured with NGF-loaded PSiO2 carriers. DRG neurons were immunostained against neurofilament H (green), enabling fluorescent imaging of the cell soma and the extending neurites. Scale bar = 50 μm. DRG cells cultured with NGF-loaded PSiO2 carriers exhibit an enhanced outgrowth tendency, similar to neurons supplemented with free NGF (c vs. b), while the untreated neurons (a) show a limited extent of neurite initiation, elongation and branching