Intranasal delivery of glucagon-like peptide-1 to the brain for obesity treatment: opportunities and challenges

Nose-to-brain (N2B) pathways can address limitations of the subcutaneous route for GLP-1 RAs. However, peptide delivery to the brain is challenging due to nasal physiological barriers and the drug's physicochemical properties. Innovative approaches, such as cell permeation enhancers, mucoadhesive systems, and nanocarriers in nasal formulations, along with efficient drug delivery devices, show promising preclinical results. Despite this, successful preclinical data does not guarantee clinical effectiveness, highlighting the need for comprehensive clinical investigations to optimize formulations and fully utilize the nose-to-brain interface for peptide delivery.