Review: clinical opportunities provided by the nasal administration of peptides

Peptides are rapidly being developed as potential new therapeutic agents and the nasal route is being evaluated as a means of achieving systemic absorption. Current research in man is being directed at a number of polypeptides, including calcitonin, growth hormone releasing hormones (GHRH), insulin, gonadotropin hormone releasing hormones (GnRH) and vasopressin analogues. The underlying protective functions of the nose provide anatomical, temporal and enzymatic barriers to absorption of peptides. The nasal route is relatively unsuccessful when used for high molecular weight polypeptides. Penetration enhancers improve bioavailability but are poorly tolerated. Reproducibility of effect is highly variable, major contributing factors including the site of deposition and type of delivery system as well as changes in the mucous secretion and mucociliary clearance, compounded by the presence of allergy, hay fever and the common cold in treated subjects. The future potential for this route lies in development of effective and well tolerated formulations in highly accurate delivery systems for the chronic administration of peptides, enabling the replacement of impractical and invasive intravenous injections in patients on lifelong substitution treatment for various deficiency states.