For the most part, peptide nasal sprays are composed of an aqueous solution or suspension with excipients (e.g., buffering agents, viscosity modifiers, emulsifiers), filled in non-pressurized dispensers with a pump that delivers a spray of up to several hundred metered doses per unit. This dosage form requires specialized formulation, container closure systems, and delivery mechanisms to ensure accurate dosing and delivery. Additionally, the design of excipients can affect the pharmacokinetic properties and overall quality of the drug product.
Intranasal administration of peptide drugs may be more effective than other routes of administration. This is based on the anatomy of the nasal route, pathways to the CNS, and the transporters involved in the process. However, the exact mechanism of IN peptide delivery to the brain remains undefined.
One potential pathway involves the orexinergic system. This is a group of neuropeptides, including orexin-A, which are decreased in people with narcolepsy and associated with cataplexies. Orexin-A was administered IN via a nasal spray in a study of narcolepsy patients to determine if it could restore orexinergic function.
Another promising approach is the use of polyethylenimine-conjugated scavenger peptides to reduce excessive electrical activity in the brain. This type of scavenger peptide works by inhibiting the neurabin molecule, which is responsible for excessive neuronal excitability. This scavenger peptide was shown to be effective in a mouse model of seizures and an Alzheimer’s disease mouse model. It is also easy to administer IN using a nasal spray.