Nasal route for direct delivery of solutes to the central nervous system: fact or fiction?

During this century, several investigators reported that certain viruses, metals, drugs, and other solutes could bypass systemic circulation and enter the brain and/or cerebrospinal fluid directly following nasal administration. Although evidence clearly suggests that the olfactory epithelium and its olfactory cells play a major role, little is known about the mechanisms of direct transport of solutes into the brain. An overview of what is known about these mechanisms may aid in further research in this field, including studies of direct drug delivery to the central nervous system. This review, in addition to summarizing the literature to date, clearly describes the intricate association of the anatomical features involved in direct entry of solutes into the brain following nasal administration. To aid in the understanding of the possible routes a solute can take after nasal administration, the anatomy of the olfactory epithelium and surrounding tissues is described, and a detailed scheme delineating the emerging pathways is presented. Techniques used in delineating these pathways and studies supporting a particular pathway are discussed in greater detail. Finally, some factors influencing the direct transport of solutes to the cerebrospinal fluid and brain are summarized.