Intranasal administration provides a method of bypassing the blood brain barrier, which separates the
systemic circulating system and central interstitial fluid, and directly delivering drugs to the central nervous system.
This method also circumvents first-pass elimination by the liver and gastrointestinal tract. In the present study, the authors
investigated intranasal siRNA delivery efficiency by using FITC-labeled transfection control siRNA and a genespecific
siRNA. The localization of fluorescence-tagged siRNA revealed that siRNA was delivered to cells in the olfactory
bulb and that the level of the siRNA target gene (alpha B-crystallin) was significantly reduced in the same area. siRNA
was delivered to processes as well as nuclei and cytoplasm. At 12 hrs after intranasal delivery, siRNA-mediated target
gene reduction was observed in other more distally located brain regions, for example, in the amygdala, entorhinal cortex,
and hypothalamus. Target gene knockdown was demonstrated by double immunohistochemistry, which demonstrated
alpha B crystallin expression depletion in more than 70% of cells at 12 hrs after the intranasal delivery. siRNA-mediated
target gene suppression was detected not only in neurons but in glia, for example, astrocytes. These results indicate
that intranasal siRNA delivery offers an efficient means of reducing specific target genes in certain regions of the brain
and of performing gene knockdown-mediated therapy.