NANOPLATFORMS CONCEIVED FOR NOSE-TO-BRAIN DRUG DELIVERY

Many approaches to brain delivery of bioactive compounds have emerged in recent years. Intranasal (IN) route is one of the newly focused delivery options for central nervous system (CNS) targeting, since this is the only way through which the brain is in connection with the outside environment. Nose-to-brain (N2B) drug delivery can be achieved by different mechanisms that are not yet fully understood. Drugs can be transported directly from the nasal cavity to the CNS by the trigeminal and the olfactory nerves pathway by passing the blood brain barrier. In order to overcome some of the limitations associated with the administration of free drugs (i.e. rapid elimination, poor water solubility, stability etc.), the use of nanomedicine could be considered a promising approach and is under intense investigation. Nanoplatforms of various nature [polymeric nanoparticles (PNP), lipid nanoparticles (SLN, NLC) nanocrystals (NCs)], characterized by different physico-chemical and technological properties have been designed to improve drug transfer after N2B delivery. Fluorescent dye (Rhodamine B) loaded PNP have been detected after IN administration in healthy rats to evaluate their distribution in brain areas. Once confirmed PNP transport to hippocampus, assessment of drug efficacy was performed after IN administration of oxcarbazepine loaded PNP (OXC_PNP) in an in vivo model of epilepsy. Our results demonstrated significant protective effects against seizures with a reduced dose and number administrations of OXC_PNP compared to the neat drug. Recently, nanocrystalline drug technology approach was also investigated to overcome one of the main limitations of colloidal systems, namely the difficulty to obtain an highly concentrated drug formulation in the small volume necessary for IN administration. NCs were formulated starting from natural (curcumin, resveratrol) and synthetic molecules (carbamazepine) obtaining concentrated formulations with high drug loading, particularly useful for for the treatment of neurodegenerative diseases by the N2B strategy. NCs have been evaluated in vitro on Olfactory Ensheating Cells, a unique class of glia that envelopes bundles of olfactory axons, that project to the olfactory bulb which we consider to play a key role in the direct pathway of drug transport through the N2B route. Overall, nanomedicine combined with IN administration is a relevant research topic that can rise as a hope for a new era of brain diseases treatment.