Nose to brain delivery: localization and time-course of polymeric nanoparticles on different regions of brain rats

The increase of neurodegenerative diseases incidence encourages academic and industrial research to investigate new strategy for drug delivery. Currently, intranasal route (IN) is exploited to bypass blood-brain barrier (BBB) and to lead to a direct delivery of the molecule into the brain (Ong et al., 2014). Due to the low therapeutic dose of free drugs that achieve brain through olfactory/trigeminal pathways, the development of drug delivery systems (DDSs) is necessary to enhance the drug transport through olfactory area. Polymeric nanocarriers (NPs) are excellent candidate to obtain local enzymatic protection, to increase residence time against mucociliar clearance and to prolong release in the target site. Several authors claimed the Central Nervous System (CNS) target of NPs after IN administration, but today none describes the possible correlation between different properties of NPs and their localization on the different region of brain. In our previous in vitro study we demonstrated that the uptake of different rhodamine labeled NPs by olfactory glial cells was influenced by the carrier charge (Musumeci et al., 2014). The aim of this work was to investigate the regions of the brain where fluorescent NPs are localized, after IN, respect to surface characteristics and mean size. We carried out an in vivo study on rats after IN administration of coated and uncoated fluorescent NPs in order to assess how the coating layer or the mean size influence the localization of nanocarriers into the brain. Chitosan coated PLGA (poly-lactic-co-glycolic acid) NPs nanosuspension was selected after a preliminary screening by photon correlation spectroscopy (PCS) and Turbiscan analyses.