ABSTRACT
Nasal delivery is increasingly considered to be an alternative route for drugs that currently require parenteral administration to achieve good efficacy, or where circumstances make oral delivery difficult. As a site for systemic absorption the nasal route provides a means of avoiding first pass metabolism, and the thin epithelia (1) with a large surface area (150 cm2) (2), combined with a high perfusion of arterial blood mean that it is ideally suited to drug absorption (3). The presence of many commercial nasal preparations already available on the market (4) confirms the patient acceptability of this route of administration. The majority of commercially available formulations however, are designed for topical treatment of conditions, such as allergic rhinitis, colds, and nasal congestion, with a few products available for systemic delivery of small peptide molecules such as desmopressin and calcitonin. Investigation of nasal absorption of larger peptide molecules, primarily insulin, has steadily continued over many years, with mixed success. Initial investigations were carried out using commercially available insulin preparations intended for subcutaneous (SC) administration, given intranasally to healthy and diabetic subjects (5). Recent research
has focused on more specialized delivery vehicles (6-9). The opportunity for utilizing nasal drug delivery for systemic effect has increasingly become the focus of research for many other therapeutic areas, with applications such as delivery of heparins (10), melatonin (11), apomorphine (12), human growth hormone (13), and combined systemic and mucosal immunization against anthrax (14,15) and influenza (16). For many therapeutic indications, an attractive advantage of the avoidance of first pass metabolism through nasal delivery is a reduction in dosage requirements, with a corresponding theoretical decrease in adverse side effects. Achieving systemic levels of nasally absorbed therapeutic compounds is dependant on a number of complex factors, and in order to understand the obstacles to nasal delivery, it is necessary to consider the physiology of the human nose.
