NASAL ROUTE FOR DIRECT DELIVERY OF SOLUTES TO THE CENTRAL-NERVOUS-SYSTEM - FACT OR FICTION

During this century, several investigators reported that certain virus es, metals, drugs, and other solutes could bypass systemic circulation and enter the brain and/or cerebrospinal fluid directly following nas al administration. Although evidence clearly suggests that the olfacto ry epithelium and its olfactory cells play a major role, little is kno wn about the mechanisms of direct transport of solutes into the brain. An overview of what is known about these mechanisms may aid in furthe r research in this field, including studies of direct drug delivery to the central nervous system. This review, in addition to summarizing t he literature to date, clearly describes the intricate association of the anatomical features involved in direct entry of solutes into the b rain following nasal administration. To aid in the understanding of th e possible routes a solute can take after nasal administration, the an atomy 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 f actors influencing the direct transport of solutes to the cerebrospina l fluid and brain are summarized.