Intranasal delivery of polymeric nanoparticles in the rat: An innovative brain targeting strategy for diseases of Central Nervous System

Nose to brain delivery, combining with polymeric nanocarriers (NPs), represents a promising non-invasive strategy to carry molecules into the brain, bypassing blood brain barrier. It's possible to increase the residence time against mucociliar clearance and to prolong the release in the target site, with appropriate NPs. We used spherical NPs with negative surface charge and with a mean size lower 250 nm suitable for nose to brain delivery. To detect the cellular distributions of NPs, a fluorescent neural marker, rhodamine B, was encapsulated into NPs observed on a fluorescence microscope. The aim of this study was to investigate in the rat the brain localization of the fluorescent NPs 8, 24 and 48 h after IN administration. Our data demonstrated that the NPs could be internalized into cells and their internalization was time and region dependent. In fact, within the initial 8 h, many fluorescence NPs were found around the cells. With the extension of time, the intracellular labeled NPs increased with regional differences in the brain. In fact, after 24 h the uptake of labeled NPs was prevalently found in the rostral regions, whereas after 48 h the uptake of the labeled NPs decreased in the rostral and increased in caudal regions of the brain. These findings support the hypothesis that therapeutic agents loaded NPs, utilized in this study, may have a direct access to the brain and can represent a very promising strategy for the diseases of the central nervous system.