Abstract
Background: The management of central nervous system diseases is extremely challenging due to the numerous obstacles that stand against the successful delivery of drugs to their target site in the brain. Defeating the blood-brain barrier is considered the most significant challenge in this delivery. Different alternative routes of administration have been investigated. Nasal delivery is one of the possible ways for direct brain targeting. The nasal mucosa is the only part of the body at which the external environment become in straight connection with the central nervous system which takes place through the olfactory portion of the nasal mucosa. Different mechanisms have been suggested to describe the pathway for straight nasal to brain transport of medications, however, the precise route is still vague. The most important proposed pathways include nerve pathways (olfactory and trigeminal nerve), vascular, lymphatic, and cerebrospinal fluid mediated pathways. Among these mechanisms, the olfactory intra-neuronal delivery is the dominant one. Various particulate systems have been investigated for nasal delivery with the intention of direct transport to the brain. The most frequently studied delivery systems are polymeric nanosystems, lipid based nanosystems, and nanometric emulsions. In conclusion, direct nasal-to-brain delivery is a very fertile research area and any achievements in this area are running side by side with the progressions that occur in the particulate systems.
