Nose to brain delivery and nanotechnology are the combination of innovative strategies for molecules to reach the brain and to bypass blood brain barriers. In this work we investigated the fate of two rhodamine B labeled polymeric nanoparticles (Z-ave <250nm) of opposite surface charge in different areas of the brain after intranasal administration in rats. A preliminary screening was carried out to select the suitable positive (chitosan/poly-l-lactide-co-glycolide) nanocarrier through photon correlation spectroscopy and turbiscan. Physico-chemical and technological characterizations of poly-l-lactide-co-glycolide (negative) and chitosan/poly-l-lactide-co-glycolide (positive) fluorescent labeled nanoparticles were performed. The animals were allocated to three groups receiving negative and positive polymeric nanoparticles via single intranasal administration or no treatment. The localization of both nanocarriers in different brain areas was detected using fluorescent microscopy. Our data revealed that both nanocarriers reach the brain and are able to persist in the brain up to 48h after intranasal administration. Surface charge influenced the involved pathways in their translocation from the nasal cavity to the central nervous system. The positive charge of nanoparticles slows down brain reaching and the trigeminal pathway is involved, while the olfactory pathway may be responsible for the transport of negatively charged nanoparticles, and systemic pathways are not excluded.

Intranasal (IN) drug delivery is recognized to be an innovative strategy to deliver drugs to the Central Nervous System. One of the main limitations of IN dosing is the low volume of drug that can be administered. Accordingly, two requirements are necessary: the drug should be active at a low dosage, and the drug solubility in water must be high enough to accommodate the required dose. Drug nanocrystals may overcome these limitations; thus, curcumin was selected as a model drug to prepare nanocrystals for potential IN administration. With this aim, we designed curcumin nanocrystals (NCs) by using Box Behnken design. A total of 51 formulations were prepared by the sonoprecipitation method. Once we assessed the influence of the independent variables on nanocrystals’ mean diameter, the formulation was optimized based on the desirability function. The optimized formulation was characterized from a physico-chemical point of view to evaluate the mean size, zeta potential, polidispersity index, pH, osmolarity, morphology, thermotropic behavior and the degree of crystallinity. Finally, the cellular uptake of curcumin and curcumin NCs was evaluated on Olfactory Ensheathing Cells (OECs). Our results showed that the OECs efficiently took up the NCs compared to the free curcumin, showing that NCs can ameliorate drug permeability.