Flavonoids in Nasal Therapeutics: Biological Activities, Delivery Challenges, and Formulation Strategies–A Systematic Review

Flavonoids represent a significant group of secondary metabolites. They have gained significant attention in the field of health due to their wide range of chemical structures and their diverse biological activities. These compounds have been most commonly administered orally as sugar conjugates (heterosides). Flavonoid nasal administration emerges as a therapeutic strategy, with potential for local, systemic, or targeted flavonoid actions, mainly in the free form (aglycones). This study provides a systematic and comprehensive review of flavonoid classes and administration routes, emphasizing their roles at three levels of the nasal administration route. Following PRISMA guidelines, a systematic search was conducted in Web of Science and PubMed (December 1997-November 2024), retrieving 225 records, of which 40 met the inclusion criteria. The first one is in the nasal cavity, highlighting its beneficial effects on the nasal mucosal epithelia (topical effect); the second is the flavonoid administration for treating naso-respiratory and other diseases, and the third is how the flavonoid can be targeted to the brain, taking advantage of the nose-to-brain route to prevent or treat CNS diseases.