Review: Clinical Opportunities Provided by the Nasal Administration of Peptides

Abstract

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.

Effects of polyamidoamine (PAMAM) dendrimers on the nasal absorption of poorly absorbable drugs in rats

“…On the other hand, there are some disadvantages with nasal drug delivery including the low permeability of the mucosa to large molecules, enzymatic degradation, the very small absorption capability of the nasal cavity, limiting application to drugs that can be supplied in small doses, and the rapid mucociliary clearance, which shortens the period of time available for efficient absorption and causes low bioavailability (Harris, 1993;Jones et al, 1997;Behl et al, 1998). Therefore, absorption enhancers, proteolytic enzyme inhibitors and suitably designed formulations have been utilized to increase the bioavailability of poorly absorbable drugs in nasal delivery systems (Morimoto et al, 1995;Dondeti et al, 1996;Davis and Illum, 2003).…”

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“…There is risk of irreversible damage of the cilia on the nasal mucosa and local side effects, both from the drug substances and from the constituents added to the dosage forms 10 .…”

“…Advantages of Nasal Route: Systemic nasal absorption of drug is a alternative to parenteral drug delivery system, as it various advantages, which include 10 :…”

Formulation and Evaluation of Ion-Activated in Situ Gel of Metoprolol Tartrate for Nasal Administration

“…Nasal administration offers an interesting alternative to the parenteral route for achieving systemic drug effects. Parenteral route may be inconvenient or oral administration may sometimes result in unacceptably low bioavailabilties 1 . The nasal epithelium is a highly permeable monolayer, the submucosa is richly vascularised and hepatic firstpass metabolism is avoided after nasal administration.…”