Intranasal drug delivery to the brain

Drug delivery into the central nervous system (CNS) compartment is often restricted by the blood–brain barrier (BBB) and blood–cerebrospinal fl uid barriers (BCSFB) that separate the blood from brain interstitial and cerebrospinal fl uids, respectively. New strategies to circumvent the BBB are greatly needed to utilize polar pharmaceuticals and large biotherapeutics for CNS disease treatment because the BBB is typically impermeable to such compounds. Intranasal administration is a noninvasive method of drug delivery that potentially allows even large biotherapeutics access to the CNS along extracellular pathways associated with the olfactory and trigeminal nerves. Rapid effects, ease of self-administration, and the potential for frequent, chronic dosing are among the potential advantages of the intranasal route. This chapter provides an overview of the unique anatomic and physiologic attributes of the nasal mucosa and its associated cranial nerves that allow small but signifi cant fractions of certain intranasally applied drugs to transfer across the nasal epithelia and subsequently be transported directly into the CNS. We also review the preclinical and clinical literature related to intranasal targeting of biotherapeutics to the CNS and speculate on future directions.