Olfaction and drug delivery to the human olfactory airspace: current challenges and recent advances

Olfactory function, despite its critical role in human survival and quality of life, is often underappreciated. This could be associated with the fact that symptoms of olfactory dysfunction rarely occur in isolation as they are frequently concomitant with comorbidities. Furthermore, effective treatments for olfactory dysfunction largely remain elusive, no standardized clinical practice for treating this dysfunction currently exist; thus, complicating the initiation of appropriate therapeutic modalities. Intranasal administration of topical medication targeting the olfactory cleft represents a safe, noninvasive and potentially efficacious approach, but several challenges impede effective drug delivery. This review highlights the importance of human olfaction, assessment of olfactory function, underlying sources of olfactory dysfunction, and challenges involved in developing long-term and effective treatment modalities, particularly in the administration of topical medication to the olfactory cleft intranasally. Advancements in both device-related and administration-related modalities designed to enhance intranasal drug delivery are discussed. Clinical management typically prioritizes comorbid conditions, relegating symptoms pertaining olfactory dysfunction to ancillary concerns. Device manufacturers for intranasal administration likewise underestimate the complexity and variabilities of the nasal cavity, and how these impact drug transport. Synergistic implementation of device and formulation strategies can potentially yield enhanced olfactory cleft drug delivery.